The role of pkcι in yap 1 signaling in cervical cancer and its relationship with prognosis

The role of pkcι in yap 1 signaling in cervical cancer and its relationship with prognosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The role of pkcι in yap 1 signaling in cervical cancer and its relationship with prognosis shengmin chen, guoping wang, zhiren lin, feng yuan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5663204/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract To explore the role of Protein Kinase Cι(PKCι/PRKCI) in yes-associated protein 1 (YAP1) signaling in cervical cancer and its relationship with prognosis. Select normal cervical tissue(NCT)low-grade squamous intraepithelial lesions(LSIL),high-grade squamous intraepithelial lesions(HSIL)and cervical squamous cell carcinoma(SCC)in 80 cases each.PKCι and YAP1 were analyzed by immunohistochemistry(IHC)and analyzed for correlation,clinical pathology and prognosis.Cervical cancer SiHa cell lines were transfected with PKCι gene overexpression,transfection efficiency was evaluated by inverted fluorescence microscope,viability was treated with PKCι inhibitor aurothiomalate,which was measured by CCK-8,and cell migration was measured by transwell experiments.The PKCι gene expression was measured by real-time reverse transcription polymerase chain reaction(qRT-PCR)and verified by transcriptome sequencing and qRT-PCR. The positivity rates for PKC ι and YAP1 varied in patients with NCT,LSIL, and HSIL ( P < 0.05). Both PKC ι and YAP1 expression showed statistically significant differences between different degrees of SCC differentiation and the presence of vasculoma plugs( P < 0.05). Univariate analysis of the survival prognosis of patients with SCC showed that protein expression,differentiation,lymph node metastasis, and vasoma metastasis were independent factors affecting overall survival( P < 0.05). The expression level of PKC ι transfected PKCι mRNA in SiHa cells was significantly higher than that in empty-loaded liposomes( P < 0.05). Patients with cervical lesions are often accompanied by abnormal expression of PKC ι and YAP1,which may have synergistic effects between each other to affect the occurrence and development of SCC and its prognosis,promote the proliferation and migration of SCC cells,and provide a possible basis for the pathogenesis study of SCC and its diagnosis and treatment to determine the prognosis. cervical carcinomalesions protein kinase Cι yes associated protein 1 human papillomavirus T cells Figures Figure 1 Figure 2 Figure 3 1. Introduction Cervical cancer is one of the most common malignant tumors in women. Studies have confirmed that human papillomavirus (HPV) infection, particularly high-risk HPV infection, is the primary cause of cervical cancer . However, only 1% of HPV infections are caused by cervical cancers. Previous studies suggested that immunosuppression is a synergistic factor. PKCι is a non-canonical protein kinase c that promotes immune suppression through the downstream effector YAP1, in YAP1 promotes tumor immune suppression by recruiting bone marrow-derived inhibitory cells and CD8 T cells. Regulation of PKC ι/YAP1 provides possible targets for cervical cancer immunotherapy, and PKCι is a non-classical PKC that has been reported that PKCι/YAP1 is involved in the occurrence and development of tumors and may provide a possible target for the diagnosis and treatment of cervical cancer[ 1 ]. 2. Materials and Methods 2.1 Materials Histological specimens of NCT, LSIL, HSIL, and SCC were obtained from our hospital after uterine surgery between January 2013 and January 2015. No anti- tumor therapy was administered and there was no significant difference in age between the groups. There were 80 patients each in the NCT, LSIL, HSIL, and SCC groups. All the cases and experimental results were confirmed by senior pathologists after reviewing the radiographs. The NCT group included gynecologic al tumor specimens obtained after total hysterectomy. All reagents (boxes) were obtained from the Shanghai Xinyu Company and used according to the manufacturer’s instructions. 2.2 Methods The IHC two-step assay was used to detect the expression levels of PKC- ι and YAP1 in four groups of tissues: rabbit anti-PKCiota antibody (batch BJ07176986) and RabbitAnti-YAP1antibody (batch AI08203707). The score was observed under an optical microscope and determined based on the percentage of positive cells and the staining intensity . This was obtained by multiplying the two scores, as follows: 0 –1 was divided into −, 2–4 into 1+, 5–8 into 2+, and 9–12 into 3+. where − is the negative group, and 1+/2+/3 + was the positive group. The first method is based on the percentage of positive cells (i.e., the number of positive cells as a percentage of the total number of cells). The details are as follows: the proportion of 0 positive cells is < 5%; The proportion of 1 positive cells is 6% ~ 25%; The proportion of 2 positive cells is 26% ~ 50%; The proportion of 3 positive cells was 51% ~ 75%; The proportion of 4 positive cells was 76–100%; The other is scored according to the intensity of cell staining, and the cell has no color 0; Light brown yellow 1 point; Brown yellow 2 points; Brown 3 points [ 2 ]. SiHa cells in the logarithmic growth phase were digested with trypsin and a cell suspension was prepared at a concentration of 1×105 cells /ml. The cells were inoculated in 96-well plates at 10,000 cells/well, 100µl medium was added to each well, and the cells were cultured in a CO 2 (5%) incubator at 37°C for 24h to adhere to the wall, and the cells were cultured without serum for 24 h. After culturing, half of the cell samples were replaced with a drug-containing medium, and the control group was replaced with a solvent-containing medium. After the treatment time reached the set time, CCK-8 solution was added to all wells and incubated in the incubator for another 2 h. Absorbance at 450 nm was measured using an enzyme analyzer. Solvent-treated cells were used as the control group and cell-free culture medium was used as the blank group. The proliferation or inhibition rate of tumor cells by the drugs was calculated using the following formula : Proliferation rate (%) = (experimental group-blank group)/(control group-blank group) × 100. Inhibition rate (%) = (control experimental group)/(control blank group) × 100. The overexpression of PRKCI gene was transfected into human cervical cancer SiHa cell line, the number and intensity of intracellular fluorescence were observed by inverted fluorescence microscope to evaluate the transfection efficiency, PRKCI inhibitor aurothiomalate was treated, and the survival rate was detected by CCK-8. Overexpression of the PRKCI gene was transfected into the human cervical cancer SiHa cell line, and the number and intensity of intracellular fluorescence were observed using an inverted fluorescence microscope to evaluate transfection efficiency. The PRKCI inhibitor aurothiomalate was used and PRKCI gene expression was detected using real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transcriptome sequencing and quantitative real-time polymerase chain reaction (qPCR) were performed. Primer sequences( Table 1 ) . Overexpression of the PRKCI gene was transfected into the human cervical cancer SiHa cell line, and the number and intensity of intracellular fluorescence were observed using an inverted fluorescence microscope to evaluate transfection efficiency. The PRKCI inhibitor aurothiomalate was used, and cell migration was detected using the transwell assay [ 3 ]. 2.3 Statistical analysis SPSS18.0 software was used to process the data, χ 2 test was used as n (%), and Spearman correlation analysis was used for correlation analysis. The Kaplan-Meier method was used for single factor analysis. Comparisons between groups were performed using the log-rank test. The Cox proportional hazards model was used for multivariate analysis. A variance homogeneity test was used to compare the rates. Differences were considered statistically significant at P < 0.05. 3. Results 3.1. Comparison of PKCι、YAP1 positive rate among groups The positive rates of PKCιI and YAP1 in patients with cervical lesions were compared with 320 tissues after IHC detection, and the results showed that the positive rates of PKCι I and YAP1 in patients with NCT, LSIL, HSIL, and SCC were higher ( P < 0.05) (Table 2 ) and༈Fig. 1– 3 ). Table 2 Comparison of PKCι、YAP1 positive rate among groups[n(%)] Group N PKCι YAPl NCT 80 5(6.250) 2(2.500) LSIL 80 8(10.000) 9(11.250) HSIL 80 27(33.750) 25(31.250) SCC 80 63(78.750) 59(73.750) χ 2 122.253 126.824 P < 0.001 < 0.001 3.2. Correlation between patient of cervical lesion and expression of PKCι、YAP Correlation analysis of cervical lesion severity and PKCι and YAP1 expression SPSSSpearman correlation analysis showed that cervical lesion severity was positively correlated with PKCι and YAP1 expression ( P < 0.05) (Table 3 ). Table 3 Correlation between patient of cervical lesion and expression of PKCι、YAP( r, P ) Correlation analysis PKCι YAP1 Cervical disease level 0.577(<0.001) 0.592(<0.001) 3.3. Correlation between patient of SCC and expression of PKCι、YAP1 Correlation between PKC-ι and YAP1 expression in SCC patients Spearman correlation analysis results showed that PKC-ι and YAP1 expression were positively correlated with each other in SCC ( P < 0.05)(Table 4 ). Table 4 Correlation between patient of SCC and expression of PKCι、YAP1(n) YAP1 - + PKCι - 11 6 + 10 53 3.4. Relationship between and protein expression and early scc clinicopathological features The relationship between PKCι and YAP1 and clinicopathologic al features of early SCC The relationship between PKC ι and YAP1 positive expression and clinicopathologic al features of early SCC showed that the positive expression of PKC ι and YAP1 was statistically different in different degrees of differentiation of SCC and whether there was a hemangioma thrombus ( P < 0.05)(Table 5 ). Table 5 Relationship between and protein expression and early scc clinicopathological features(n) PKCι YAP1 - + - + Age(year) <35 6 14 4 16 ≥ 35 11 49 17 43 Lymphatic metastasis No 6 67 5 68 Yes 1 6 2 5 Degree of differentiation Low 7 3 6 4 Middle-high 10 60 15 55 FIGO staging Ⅰb 11 28 11 28 Ⅱa 6 35 10 31 Vein tumor thrombus No 13 25 15 23 Yes 4 38 6 36 3.5. PKCι, YAP1 and the prognosis of patients with early SCC 3.5.1 Analysis of kaplan-meier single factor in prognosis of early scc patients Univariate analysis In the analysis of survival and prognosis of patients with early SCC, univariate analysis showed that the expression of various proteins, the degree of differentiation, lymph node metastasis, and the condition of vascular tumor embolus were independent factors affecting the overall survival and prognosis ( P < 0.05)(Table 6 ). Table 6 Analysis of kaplan-meier single factor in prognosis of early scc patients(%) Factor N Five-year survival rate P Age(year) <35 20 16(80.0) 0.233 ≥ 35 60 49(81.6) Lymphatic metastasis No 73 61(83.5) 0.035 Yes 7 5(71.4) Degree of differentiation Low 10 7(70.0) 0.032 Middle-high 70 58(82.8) FIGO staging Ⅰb 39 30(76.9) 0.104 Ⅱa 41 30(73.1) Vein tumor thrombus No 38 31(81.5) 0.031 Yes 42 32(76.1) PKCι No 17 15(88.2) 0.037 Yes 63 50(79.3) YAP1 No 21 19(90.4) 0.029 Yes 59 46(77.9) 3.5.2 Cox Multivariate Analysis The expression of proteins, differentiation degree, lymph node metastasis, vascular tumor embolus and FIGO staging, which were statistically significant in univariate analysis, were incorporated into the Cox proportional risk model.The results showed that protein expression and lymph node metastasis were independent factors affecting the 5-year survival rate of patients. Among them, high expression of PKCι and YAP1 proteins and lymph node metastasis were risk factors(Table 7 ). Table 7 Analysis of Cox many factors in prognosis of early scc patients Factor HR 95%CI P minimum maximum Age(year) 3.987 0.504 31.539 0.190 Lymphatic metastasis 5.895 1.428 24.343 0.014 Degree of differentiation 2.919 0.659 12.925 0.158 FIGO staging 4.329 0.510 36.731 0.179 Vein tumor thrombus 0.410 0.184 0.914 0.029 PKCι 26.217 3.374 203.723 0.002 YAP1 3.261 1.266 8.3999 0.014 3.6. CCK-8 detection The survival rate was detected using CCK-8, and the difference was statistically significant ( P < 0.05), indicating that PKCι promoted SCC cell proliferation(Table 8 ). Table 8 CCK-8 assay was used to detect the cell proliferation level (N = 1, SiHa cells) Group 1 2 3 4 5 6 mean SD proliferation rate SD(%) NC 0.602 0.680 0.596 0.662 0.658 0.626 0.640 0.038 100.000 5.947 pcDNA-NC 0.607 0.620 0.627 0.643 0.663 0.619 0.632 0.022 98.812 3.386 pcDNA-PRKCI 0.793 0.831 0.825 0.904 0.916 0.863 0.854 0.053 133.490 8.359 Aurothiomalate Processing 24h (25µM) 0.469 0.477 0.517 0.413 0.413 0.413 0.458 0.045 71.576 6.998 3.7. QRT-PCR assay was used to verify the expression level The expression level of PKCι mRNA in SiHa cells in the PKCι transfection group was significantly increased by qPCR, and the difference was statistically significant compared with the difference homogeneity test in the no-loaded liposome group ( P < 0.05)(Table 9 ). Table 9 QRT-PCR assay was used to verify the expression level(N = 3) PKC mean SD YAP1 mean SD 1.00 1.03 0.07 1.00 0.98 0.06 0.99 0.91 1.11 1.03 1.03 1.07 0.09 1.02 1.02 0.07 1.17 0.95 1.00 1.10 3.05 3.14 0.14 2.64 2.49 0.15 3.30 2.47 3.07 2.35 0.54 0.51 0.04 0.64 0.63 0.06 0.53 0.57 0.47 0.69 3.8. Comparison of cell migration levels by transwell assay Transwell test was used to detect cell migration, and the difference in variance homogeneity test was statistically significant ( P < 0.05), indicating that PKCι could promote SCC cell migration(Table 10 )and༈Fig. 3 ༉. Table 10 Comparison of cell migration levels by transwell assay(N = 3, SiHa cells) Group 1 2 3 1 2 3 1 2 3 mean SD NC 255 251 238 269 238 242 258 248 243 249.111 10.301 pcDNA-NC 236 255 247 265 232 248 239 260 243 247.222 11.088 pcDNA-PRKCI 384 360 374 378 356 386 385 377 350 372.222 13.498 Aurothiomalate Processing 24h(25µM) 144 143 150 149 130 142 137 141 155 143.444 7.401 4. Discussion The molecular mechanism underlying cervical cancer is caused by persistent infection with high-risk HPV requires further clarification and revealed. Most people infected with HPV can clear the virus themselves, whereas a small number of persistently infected people will further develop and even progress from cervical intraepithelial neoplasia to cervical cancer[ 4 ]. PKC ι(also known as PRKCΙ) is an atypical PKC (aPKC, including ζ, ι/λ). aPKC plays an important role in the development of tissues and organs, maintenance of homeostasis, tumorigenesis and development, and immune responses by regulating multiple signaling pathways[ 5 – 7 ]. Studies have shown that PKCι signaling inhibitors inhibit two key oncogenic signaling pathways, driven by PKCι and KCζ, to significantly reduce tumor growth and metastasis, and inhibition of atypical PKC signaling is a promising therapeutic strategy for the treatment of tumors[ 8 – 9 ]. Research has shown that PKC ι expresses a shaped immune inhibitory tumor microenvironment, which is caused by IL6/1 b, CSF3, Prostaglandin endoperoxide synthase(PTGS2) and tumor necrosisfactor-α (TNF-α) overexpression, while NK cell infiltration is decreased[ 10 – 11 ]. Studies have shown that TNF-α has bidirectional anti-cancer and pro-cancer effects, and the anti-cancer effect is manifested in that TNF-α is the most active cytokine in its anti-cancer activity.The anti-tumor mechanism of TNF-α is multi-dimensional, including inducing apoptosis, affecting the tumor vascular system, and enhancing host immunity[ 12 ]. This pro-cancer effect is reflected in the fact that TNF-α also plays a role in promoting tumor growth. In ovarian cancer cells, TNF-α upregulates inflammatory cytokines and chemokine networks, acts on the ovarian cancer microenvironment, affects tumor vascular development and cancer cell migration,and promotes tumor development and deterioration[ 13 ]. Studies have shown that PKCι promotes immunosuppression through YAP1, a downstream effector of tumor progression.YAP1 promotes tumor immunosuppression by recruiting myeloid-derived suppressorcells (MDSCs) and CD8 + T cells in the bone marrow. Owing to its low cytotoxic T cell infiltration, PKCι/YAP1 regulation provides a therapeutic strategy for highly lethal malignancies[ 14 – 15 ]. To explore the involvement of PKCι/YAP1 in the development of SCC.Pearson correlation analysis was conducted, and the results showed that cervical lesion grade was positively correlated with the positive expression of PKCι and YAP1 proteins. It was positively correlated with the expression of PKCι and YAP1. A positive correlation was observed between the PKCι levels. The expression of PKCι and YAP1 in SCC was positively correlated with each other. The positive expression of PKCι and YAP1 in SCC was statistically different at different degrees of differentiation with or without hemangioma thrombolus. Univariate analysis showed that the expression of various proteins, differentiation degree, lymph node metastasis and vascular tumor embolus were independent factors affecting the overall survival and prognosis. The expression of various proteins and lymph node metastasis in patients with SCC are independent factors affecting the 5-year survival rate of patients, in which high expression of PKCι and YAP1 proteins and lymph node metastasis are risk factors. This study suggests that the occurrence and development of cervical cancer may be related to the overexpression of PKCι and YAP1 proteins, and that there may be a synergistic effect on the occurrence and development of SCC and its prognosis. In summary, the abnormal expression of PKCι and YAP1 proteins in patients with SCC may be related to the occurrence, development and prognosis of SCC, which may provide a possible basis for the study of the pathogenesis, diagnosis and treatment of SCC, as well as for prognosis. 5. Conclusion In this study, differences in the expression of NCT, LSIL, HSIL, SCC, PKCι, and YAPl and the correlation between PKC ι and YAP1 protein expression and clinicopathological features of patients with cervical lesions were explored, and prognosis was analyzed to provide a possible basis for the study of the pathogenesis, diagnosis, and treatment of SCC and prognosis. Abbreviations PKCι/PRKCI=Protein Kinase Cι,YAP1=yes-associated protein 1,NCT=normal cervical tissue,LSIL=low-grade squamous intraepithelial lesions,HSIL=high-grade squamous intraepithelial lesions,SCC=cervical squamous cell carcinoma,IHC=immunohistochemistry,qRT-PCR=real-time reverse transcription polymerase chain reaction,HPV=human papillomavirus,PTGS2=Prostaglandin endoperoxide synthase, TNF-α=tumor necrosisfactor-α,MDSCs=myeloid-derived suppressorcells. Declarations Acknowledgments All authors thank their colleagues and patients at the Affiliated Haikou Hospital of Xiangya Medical College,Central South University. We thank Paperpal (https://preflight.paperpal.com) for English language review of this manuscript. This study was reviewed and approved by the Ethics Committee of Haikou Hospital Affiliated to Xiangya Medical College of Central South University (approval number: 2022- (ethics review) -230), and informed consent was not required for approval by the Ethics Committee. Correspondence: Haikou Affiliated Hospital of Central South University Xiangya School of Medicine,Haikou Hainan 570208,China (e-mail: [email protected] ). Corresponding author]Feng Yuan; e-mail: [email protected] . Copyright © 2024 author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Author contributions Conceptualization: Shengmin Chen. Data curation: Shengmin Chen. Formal analysis: Feng Yuan. Funding acquisition:Shengmin Chen. Investigation: Shengmin Chen. Methodology: Shengmin Chen, Guoping Wang,and Zhiren Lin. Project administration: Feng Yuan. Resources: Feng Yuan. Software: Shengmin Chen, Guoping Wang,and Zhiren Lin. Validation: Shengmin Chen, Guoping Wang,and Zhiren Lin. Visualization: Shengmin Chen, Guoping Wang,and Zhiren Lin. Writing – original draft: Shengmin Chen. Writing – review and editing:Feng Yuan. Data Access Statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Conflict of Interest Declaration: Written informed consent for participation was not required for this study, in accordance with national legislation and institutional requirements. The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript. References Sharmistha Sarkar,Christopher A.Bristow,Prasenjit Dey,et al.PRKCI promotes immune suppression in ovarian cancer[J].GENES&DEVELOPMENT,2017,31:1109–1121.doi:10.1101/gad.296640.117.[PubMed] CHEN Shengmin, WANG Guoping, LIN Zhiren, et al. Expression of PKCι/YAP1 in Cervical Cancer and Its Clinical Significance[J]. Zhong Liu Fang Zhi Yan Jiu, 2021, 48(10): 970-973.[CrossRef] Sichero,Laura,Rollison,Dana E,Amorrortu,Rossybelle P,et al.Beta Human Papillomavirus and Associated Diseases[J].Acta Cytologica,2019:1-9.doi:10.1159/000492659.[PubMed] Gilkey,Melisa B,Margolis,Marjorie A.Human Papillomavirus Vaccination Coverage Gaps in Young Adolescents[J].The Journal of Infectious Diseases,2019:727-729.doi:10.1093/infdis/jiy683.[PubMed] Hanbazazh Mehenaz,Gyure Kymberly A.Ocular Human Papillomavirus Infections[J].Archives of Pathology&Laboratory Medicine,2018:706-710.doi:10.5858/arpa.2017-0571-RA.[PubMed] Kawano T, Inokuchi J, Eto M, Murata M, Kang JH. Activators and Inhibitors of Protein Kinase C (PKC): Their Applications in Clinical Trials. Pharmaceutics. 2021 Oct 20;13(11):1748. doi: 10.3390/pharmaceutics13111748. [PubMed] Ubba V, Gupta RK, Hakim BA, Bora HK, Sachdev M, Tripathi R, Jha RK. PKC-βII is downregulated in the premature ovarian failure SD rat model. Reprod Biol. 2023 Jun;23(2):100754. doi: 10.1016/j.repbio.2023.100754.[PubMed] Harden,Mallory E,Munger,Karl.HUMAN PAPILLOMAVIRUS MOLECULAR BIOLOGY[J].Mutation Research/Reviews in Mutation Research,2016:S1383574216300679.doi:10.1016/j.mrrev.2016.07.002.[PubMed] Schiffman,Mark,Doorbar,John,Wentzensen,Nicolas,et al.Carcinogenic human papillomavirus infection[J].Nature Reviews Disease Primers,2016:16086.doi:10.1038/nrdp.2016.86.[PubMed] Pearsall,Elizabeth A.Connor,Kip M.Atypical Protein Kinase C[J].The American Journal of Pathology,2018:2142-2146.doi:10.1016/j.ajpath.2018.07.006.[PubMed] Parker,Peter J,Justilien,Verline,Riou,et al.Atypical Protein Kinase Cι as a human oncogene and therapeutic target[J].Biochemical Pharmacology,2014:1-11.doi:10.1016/j.bcp.2013.10.023.[PubMed] Parker PJ, Justilien V, Riou P, Linch M, Fields AP. Atypical protein kinase Cι as a human oncogene and therapeutic target[J]. Biochem Pharmacol. 2014 Mar 1;88(1):1-11. doi: 10.1016/j.bcp.2013.10.023.[PubMed] Qiu S, Zhang K, Chen S, Yin S. Circular RNA PRKCI (hsa_circ_0067934): a potential target in the pathogenesis of human malignancies. Front Oncol. 2024 Apr 29;14:1365032. doi: 10.3389/fonc.2024.1365032.[PubMed] Fields AP, Ali SA, Murray NR. Oncogenic PKCι decides tumor-initiating cell fate. Cell Cycle. 2016 Sep 16;15(18):2383-4. doi: 10.1080/15384101.2016.1194624.[PubMed] Wu Z, Huang C, Li R, Li H, Lu H, Lin Z. PRKCI Mediates Radiosensitivity via the Hedgehog/GLI1 Pathway in Cervical Cancer. Front Oncol. 2022 Jun 16;12:887139. doi: 10.3389/fonc.2022.887139.[PubMed] Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5663204","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":392138352,"identity":"4a5aeb0f-d1fc-4db9-bfa9-4761803bdfd2","order_by":0,"name":"shengmin chen","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"shengmin","middleName":"","lastName":"chen","suffix":""},{"id":392138353,"identity":"cc54335b-7fc2-47a4-89b8-f7cca136a2a4","order_by":1,"name":"guoping wang","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"guoping","middleName":"","lastName":"wang","suffix":""},{"id":392138354,"identity":"c83d4d7a-60db-42e4-a57b-2d432a593fa4","order_by":2,"name":"zhiren lin","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"zhiren","middleName":"","lastName":"lin","suffix":""},{"id":392138355,"identity":"8df8eda2-6744-4a3c-a91f-5fd9a9761f11","order_by":3,"name":"feng yuan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAy0lEQVRIiWNgGAWjYBACfvn3Dw58+GHDw9jeQKQWyYYcxoMze9JkmHsOEKnF4EAO82EetkM27DMSiHXZgbMHDvPwHODhnfl44w2GGptogjoYG/sSDs6xuMMjOTut2ILhWFpuAyEtzMxAt73hecZjODvHTIKx4TBhLWxsQC08bId57G+eIVILDw+PwUGQFsYZPERqkZBgSwAFMg9jD9AvCcT4xf4G8+EPwKi0Z2w/vPHGhxobwlqQgYFEAinKIVpI1TEKRsEoGAUjAwAARGFDR168TtUAAAAASUVORK5CYII=","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"feng","middleName":"","lastName":"yuan","suffix":""}],"badges":[],"createdAt":"2024-12-17 15:38:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5663204/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5663204/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72291560,"identity":"33e8286d-1067-4f57-9c79-d4cdb6e522b7","added_by":"auto","created_at":"2024-12-24 17:29:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2153335,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePositive of expression of PKCιin SCC\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5663204/v1/a100d63926d37131953428a2.png"},{"id":72291559,"identity":"e96b1901-1b10-45c6-b8a7-1aa08aae2ae8","added_by":"auto","created_at":"2024-12-24 17:29:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2001000,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePositive of expression of YAP1 in SCC\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5663204/v1/c5265f5a0cd7bc7b73b9a99c.png"},{"id":72291561,"identity":"2886c7c5-7ad5-45e2-91df-0429c536c6f0","added_by":"auto","created_at":"2024-12-24 17:29:11","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":145212,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ecell migration (crystal violet stainingX200)\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-5663204/v1/f7130a6510b673fd103537bb.png"},{"id":72535338,"identity":"3bc103ed-2a73-4a9f-94af-0343a011ce43","added_by":"auto","created_at":"2024-12-29 03:01:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5051728,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5663204/v1/45a95548-b03d-487a-b24c-d7744b2f4bcc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The role of pkcι in yap 1 signaling in cervical cancer and its relationship with prognosis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eCervical cancer is one of the most common malignant tumors in women. Studies have confirmed that human papillomavirus (HPV) infection, particularly high-risk HPV \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003einfection, is the primary cause of cervical cancer\u003c/span\u003e. However, only 1% of HPV infections are \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ecaused by\u003c/span\u003e cervical cancers. Previous studies suggested that immunosuppression is a synergistic factor. PKCι is a non-canonical protein kinase c that promotes immune suppression through the downstream effector YAP1, in YAP1 promotes tumor immune suppression by recruiting bone marrow-derived inhibitory cells and CD8 T cells. \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eRegulation of PKC\u003c/span\u003eι/YAP1 provides possible targets for cervical cancer immunotherapy, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand PKCι\u003c/span\u003e is a non-classical PKC that has been reported that PKCι/YAP1 is involved in the occurrence and development of tumors and may provide a possible target for the diagnosis and treatment of cervical cancer[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003cp\u003e2.1 Materials\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003cp\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eHistological specimens of\u003c/span\u003e NCT, LSIL, HSIL, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand SCC were obtained from our hospital after uterine surgery between January 2013 and January 2015. No anti-\u003c/span\u003etumor therapy was administered and there was no significant difference in age between the groups. There were 80 patients each \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ein\u003c/span\u003e the NCT, LSIL, HSIL, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand SCC groups. All the cases and experimental results were confirmed by senior pathologists after reviewing the radiographs. The NCT group\u003c/span\u003e included gynecologic\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eal tumor specimens obtained after total hysterectomy. All reagents (boxes) were obtained from the Shanghai Xinyu Company and\u003c/span\u003e used according to the manufacturer\u0026rsquo;s instructions.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e2.2 Methods\u003c/h2\u003eThe IHC two-step assay was used to detect \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ethe expression levels of PKC-\u003c/span\u003e\u0026iota; and YAP1 in four groups of tissues: rabbit anti-PKCiota \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eantibody (batch BJ07176986) and RabbitAnti-YAP1antibody (batch AI08203707). The score was observed under an optical microscope and determined based on the percentage of positive cells and the staining intensity\u003c/span\u003e. This was obtained by multiplying the two scores, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eas follows: 0\u003c/span\u003e\u0026ndash;1 was divided into \u0026minus;, 2\u0026ndash;4 into 1+, 5\u0026ndash;8 into 2+, and 9\u0026ndash;12 into 3+. where \u0026minus;\u0026thinsp;is the negative group, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand 1+/2+/3\u0026thinsp;+\u0026thinsp;was the positive group.\u003c/span\u003e The first \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003emethod is based on the percentage of positive cells (i.e., the number of positive cells as a percentage of the total number of cells). The details are as follows: the proportion of 0 positive cells is \u0026lt;\u0026thinsp;5%; The proportion of 1 positive cells is 6% ~ 25%; The proportion of 2 positive cells is 26% ~ 50%; The proportion of 3 positive cells was 51% ~ 75%; The proportion of 4 positive cells was 76\u0026ndash;100%; The other is scored according to the intensity of cell staining, and the cell has no color 0; Light brown yellow 1 point; Brown yellow 2 points; Brown 3 points\u003c/span\u003e[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]. SiHa cells in the logarithmic growth phase were digested with trypsin and a cell suspension was prepared at a concentration of 1\u0026times;105 cells /ml. The cells were inoculated in 96-well plates at 10,000 cells/well, 100\u0026micro;l medium was added to each well, and the cells were cultured in a CO\u003csub\u003e2\u003c/sub\u003e (5%) incubator at 37\u0026deg;C for 24h to adhere to the wall, and the cells were cultured without serum for 24 h. After culturing, half of the cell samples were replaced with \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ea drug-containing medium, and the control group was replaced with a solvent-containing medium. After the treatment time reached the set time, CCK-8 solution was added to all\u003c/span\u003e wells and incubated in the incubator for another 2 h. Absorbance at 450 \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003enm was measured\u003c/span\u003e using an enzyme analyzer. Solvent-treated cells were used as \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ethe control group\u003c/span\u003e and cell-free culture medium was used as \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ethe blank group. The proliferation or inhibition rate of tumor cells by the drugs was calculated using the following formula\u003c/span\u003e: Proliferation rate \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e(%) = (experimental group-blank group)/(control group-blank group)\u003c/span\u003e \u0026times; 100. Inhibition rate \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e(%) = (control\u003c/span\u003e experimental group)/(control blank group) \u0026times; 100. The overexpression of PRKCI gene was transfected into human cervical cancer SiHa cell line, the number and intensity of intracellular fluorescence were observed by inverted fluorescence microscope to evaluate the transfection efficiency, PRKCI inhibitor aurothiomalate was treated, and the survival rate was detected by CCK-8. Overexpression of \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ethe PRKCI gene was transfected into the human cervical cancer SiHa cell line, and the number and intensity of intracellular fluorescence were observed using\u003c/span\u003e an inverted fluorescence microscope to evaluate \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003etransfection efficiency. The PRKCI inhibitor aurothiomalate was used and PRKCI gene expression was detected using real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transcriptome sequencing and quantitative real-time\u003c/span\u003e polymerase chain reaction \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003e(qPCR) were performed. Primer sequences(\u003c/span\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e)\u003c/span\u003e. Overexpression of \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ethe PRKCI gene was transfected into the human cervical cancer SiHa cell line, and the number and intensity of intracellular fluorescence were observed using\u003c/span\u003e an inverted fluorescence microscope to evaluate \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003etransfection efficiency. The PRKCI inhibitor aurothiomalate was used, and cell migration was detected using the transwell assay\u003c/span\u003e[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e].\u0026nbsp;2.3 Statistical analysis\u003cbr\u003e\u003cimg src=\"https://myfiles.space/user_files/122228_c8a1650c59388082/122228_custom_files/img1734685101.png\"\u003e\u003cbr\u003e\n \u003cp\u003eSPSS18.0 software was used to process the data, \u0026chi;\u003csup\u003e2\u003c/sup\u003e test was used as n (%), and Spearman correlation analysis was used for correlation analysis. \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eThe Kaplan-Meier method was used for single factor analysis. Comparisons between groups\u003c/span\u003e were performed \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eusing\u003c/span\u003e the log-rank \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003etest. The Cox proportional hazards model was used for multivariate analysis. A\u003c/span\u003e variance homogeneity test was used to compare \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ethe rates. Differences\u003c/span\u003e were considered statistically significant at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003cbr\u003e\n\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Comparison of PKCι、YAP1 positive rate among groups\u003c/h2\u003e \u003cp\u003eThe positive rates of PKCιI and YAP1 in patients with cervical lesions were compared with 320 tissues after IHC detection, and the results showed that the positive rates of PKCι\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eI\u003c/span\u003e and YAP1 in patients with NCT, LSIL, HSIL, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand SCC were higher\u003c/span\u003e (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and༈Fig.\u0026nbsp;1\u0026ndash;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of PKCι、YAP1 positive rate among groups[n(%)]\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePKCι\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYAPl\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNCT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(6.250)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(2.500)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8(10.000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9(11.250)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHSIL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(33.750)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25(31.250)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63(78.750)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59(73.750)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e122.253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e126.824\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Correlation between patient of cervical lesion and expression of PKCι、YAP\u003c/h2\u003e \u003cp\u003eCorrelation analysis of cervical lesion severity and PKCι and YAP1 expression SPSSSpearman correlation analysis showed that cervical lesion severity was positively correlated with PKCι and YAP1 expression (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between patient of cervical lesion and expression of PKCι、YAP(\u003cem\u003er, P\u003c/em\u003e)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorrelation analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePKCι\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYAP1\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervical disease level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.577(\u0026lt;0.001)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.592(\u0026lt;0.001)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Correlation between patient of SCC and expression of PKCι、YAP1\u003c/h2\u003e \u003cp\u003eCorrelation between PKC-ι and YAP1 expression in SCC patients Spearman correlation analysis results showed that PKC-ι and YAP1 expression were positively correlated with each other in SCC (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)(Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCorrelation between patient of SCC and expression of PKCι、YAP1(n)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eYAP1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePKCι\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e+\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e53\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Relationship between and protein expression and early scc clinicopathological features\u003c/h2\u003e \u003cp\u003eThe relationship between PKCι and YAP1 and clinicopathologic\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eal features of early SCC The relationship between PKC\u003c/span\u003eι and YAP1 positive expression and clinicopathologic\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eal features of early SCC showed that the positive expression of PKC\u003c/span\u003eι and YAP1 was statistically different in different degrees of differentiation of SCC and whether there was a hemangioma thrombus (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)(Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRelationship between and protein expression and early scc clinicopathological features(n)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003ePKCι\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003eYAP1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge(year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLymphatic metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDegree of differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiddle-high\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFIGO\u003c/p\u003e \u003cp\u003estaging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eⅠb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eⅡa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVein tumor thrombus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5. PKCι, YAP1 and the prognosis of patients with early SCC\u003c/h2\u003e \u003cdiv id=\"Sec13\" class=\"Section3\"\u003e \u003ch2\u003e\u003cb\u003e3.5.1 Analysis of kaplan-meier single factor in prognosis of early scc patients\u003c/b\u003e\u003c/h2\u003e \u003cp\u003eUnivariate analysis In the analysis of survival and prognosis of patients with early SCC, univariate analysis showed that the expression of various proteins, the degree of differentiation, lymph node metastasis, and the condition of vascular tumor embolus were independent factors affecting the overall survival and prognosis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)(Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnalysis of kaplan-meier single factor in prognosis of early scc patients(%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFactor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFive-year survival rate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge(year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16(80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.233\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49(81.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLymphatic metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61(83.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(71.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDegree of differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(70.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiddle-high\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58(82.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFIGO\u003c/p\u003e \u003cp\u003estaging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eⅠb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30(76.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.104\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eⅡa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30(73.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVein tumor thrombus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31(81.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e32(76.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePKCι\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15(88.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50(79.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eYAP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19(90.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46(77.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e3.5.2 Cox Multivariate Analysis\u003c/h2\u003e \u003cp\u003eThe expression of proteins, differentiation degree, lymph node metastasis, vascular tumor embolus and FIGO staging, which were statistically significant in univariate analysis, were incorporated into the Cox proportional risk model.The results showed that protein expression and lymph node metastasis were independent factors affecting the 5-year survival rate of patients. Among them, high expression of PKCι and YAP1 proteins and lymph node metastasis were risk factors(Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnalysis of Cox many factors in prognosis of early scc patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFactor\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eminimum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003emaximum\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.987\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.504\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.539\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.190\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphatic metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.895\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.343\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of differentiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.919\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.659\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.925\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.158\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIGO\u003c/p\u003e \u003cp\u003estaging\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.510\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36.731\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.179\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVein tumor thrombus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.184\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.914\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePKCι\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.217\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e203.723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYAP1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.266\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.3999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.6. CCK-8 detection\u003c/h2\u003e \u003cp\u003eThe survival rate was detected using CCK-8, and the difference was statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), indicating that PKCι promoted SCC cell proliferation(Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCCK-8 assay was used to detect the cell proliferation level (N\u0026thinsp;=\u0026thinsp;1, SiHa cells)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003emean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eproliferation rate\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSD(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.602\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.680\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.596\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.662\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.626\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.640\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e100.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e5.947\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epcDNA-NC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.620\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.627\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.643\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.663\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.619\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.632\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e98.812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e3.386\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epcDNA-PRKCI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.793\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.831\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.825\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.904\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.916\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.863\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.854\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e133.490\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e8.359\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAurothiomalate\u003c/p\u003e \u003cp\u003eProcessing 24h\u003c/p\u003e \u003cp\u003e(25\u0026micro;M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.469\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.477\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.458\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e71.576\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e6.998\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.7. QRT-PCR assay was used to verify the expression level\u003c/h2\u003e \u003cp\u003eThe expression level of PKCι mRNA in SiHa cells in the PKCι transfection group was significantly increased by qPCR, and the difference was statistically significant compared with the difference homogeneity test in the no-loaded liposome group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05)(Table\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQRT-PCR assay was used to verify the expression level(N\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePKC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003emean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYAP1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003emean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.91\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e1.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e3.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e2.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e3.8. Comparison of cell migration levels by transwell assay\u003c/h2\u003e \u003cp\u003eTranswell test was used to detect cell migration, and the difference in variance homogeneity test was statistically significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), indicating that PKCι could promote SCC cell migration(Table\u0026nbsp;\u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e10\u003c/span\u003e)and༈Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e༉.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab10\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of cell migration levels by transwell assay(N\u0026thinsp;=\u0026thinsp;3, SiHa cells)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"12\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003emean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e238\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e238\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e258\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e248\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e249.111\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e10.301\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epcDNA-NC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e255\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e247\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e265\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e248\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e247.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e11.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epcDNA-PRKCI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e384\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e360\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e378\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e356\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e386\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e385\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e377\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e350\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e372.222\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e13.498\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAurothiomalate\u003c/p\u003e \u003cp\u003eProcessing 24h(25\u0026micro;M)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e149\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e142\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e141\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003e143.444\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e7.401\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe molecular mechanism underlying cervical cancer is caused by persistent infection with high-risk HPV requires further clarification and revealed. Most people infected with HPV can clear the virus themselves, whereas a small number of persistently infected people will further develop and even progress from cervical intraepithelial neoplasia to cervical cancer[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. PKC ι(also known as PRKCΙ) is an atypical PKC (aPKC, including ζ, ι/λ). aPKC plays an important role in the development of tissues and organs, maintenance of homeostasis, tumorigenesis and development, and immune responses by regulating multiple signaling pathways[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Studies have shown that PKCι signaling inhibitors inhibit two key oncogenic signaling pathways, driven by PKCι and KCζ, to significantly reduce tumor growth and metastasis, and inhibition of atypical PKC signaling is a promising therapeutic strategy for the treatment of tumors[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Research has shown that PKC ι expresses a shaped immune inhibitory tumor microenvironment, which is caused by IL6/1 b, CSF3, Prostaglandin endoperoxide synthase(PTGS2) and tumor necrosisfactor-α (TNF-α) overexpression, while NK cell infiltration is decreased[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Studies have shown that TNF-α has bidirectional anti-cancer and pro-cancer effects, and the anti-cancer effect is manifested in that TNF-α is the most active cytokine in its anti-cancer activity.The anti-tumor mechanism of TNF-α is multi-dimensional, including inducing apoptosis, affecting the tumor vascular system, and enhancing host immunity[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This pro-cancer effect is reflected in the fact that TNF-α also plays a role in promoting tumor growth. In ovarian cancer cells, TNF-α upregulates inflammatory cytokines and chemokine networks, acts on the ovarian cancer microenvironment, affects tumor vascular development and cancer cell migration,and promotes tumor development and deterioration[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Studies have shown that PKCι promotes immunosuppression through YAP1, a downstream effector of tumor progression.YAP1 promotes tumor immunosuppression by recruiting myeloid-derived suppressorcells (MDSCs) and CD8\u0026thinsp;+\u0026thinsp;T cells in the bone marrow. Owing to its low cytotoxic T cell infiltration, PKCι/YAP1 regulation provides a therapeutic strategy for highly lethal malignancies[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. To explore the involvement of PKCι/YAP1 in the development of SCC.Pearson correlation analysis was conducted, and the results showed that cervical lesion grade was positively correlated with the positive expression of PKCι and YAP1 proteins. It was positively correlated with the expression of PKCι and YAP1. A positive correlation was observed between the PKCι levels. The expression of PKCι and YAP1 in SCC was positively correlated with each other. The positive expression of PKCι and YAP1 in SCC was statistically different at different degrees of differentiation with or without hemangioma thrombolus. Univariate analysis showed that the expression of various proteins, differentiation degree, lymph node metastasis and vascular tumor embolus were independent factors affecting the overall survival and prognosis. The expression of various proteins and lymph node metastasis in patients with SCC are independent factors affecting the 5-year survival rate of patients, in which high expression of PKCι and YAP1 proteins and lymph node metastasis are risk factors. This study suggests that the occurrence and development of cervical cancer may be related to the overexpression of PKCι and YAP1 proteins, and that there may be a synergistic effect on the occurrence and development of SCC and its prognosis. In summary, the abnormal expression of PKCι and YAP1 proteins in patients with SCC may be related to the occurrence, development and prognosis of SCC, which may provide a possible basis for the study of the pathogenesis, diagnosis and treatment of SCC, as well as for prognosis.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eIn this study, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003edifferences in the expression\u003c/span\u003e of NCT, LSIL, HSIL, SCC, PKCι, and YAPl \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand the correlation between PKC\u003c/span\u003eι and YAP1 protein expression and clinicopathological features of patients with cervical lesions were explored, and prognosis was analyzed to provide a possible basis for the study of the pathogenesis, diagnosis, \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand treatment of SCC and\u003c/span\u003e prognosis.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePKC\u0026iota;/PRKCI=Protein Kinase C\u0026iota;,YAP1=yes-associated protein 1,NCT=normal cervical tissue,LSIL=low-grade squamous intraepithelial lesions,HSIL=high-grade squamous intraepithelial lesions,SCC=cervical squamous cell carcinoma,IHC=immunohistochemistry,qRT-PCR=real-time reverse transcription polymerase chain reaction,HPV=human papillomavirus,PTGS2=Prostaglandin endoperoxide synthase, TNF-\u0026alpha;=tumor necrosisfactor-\u0026alpha;,MDSCs=myeloid-derived suppressorcells.\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors thank their colleagues and patients at the Affiliated Haikou Hospital of Xiangya Medical College,Central South University. We thank Paperpal (https://preflight.paperpal.com) for English language review of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was reviewed and approved by the Ethics Committee of Haikou Hospital Affiliated to Xiangya Medical College of Central South University (approval number: 2022- (ethics review) -230), and informed consent was not required for approval by the Ethics Committee.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCorrespondence:\u0026nbsp;Haikou Affiliated Hospital of Central South University\u0026ensp;Xiangya School of Medicine,Haikou Hainan 570208,China (e-mail: [email protected]). Corresponding author]Feng Yuan; e-mail:[email protected].\u003c/p\u003e\n\u003cp\u003eCopyright \u0026copy; 2024 author(s). Published by Wolters Kluwer Health, Inc.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis is an open access article distributed under the Creative Commons\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAttribution License 4.0 (CCBY), which permits unrestricted use, distribution,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eand reproduction in any medium, provided the original work is properly\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ecited.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: Shengmin Chen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData curation: Shengmin Chen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFormal analysis: Feng Yuan.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding acquisition:Shengmin Chen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInvestigation: Shengmin Chen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMethodology: Shengmin Chen, Guoping Wang,and Zhiren Lin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eProject administration: Feng Yuan.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eResources: Feng Yuan.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSoftware: Shengmin Chen, Guoping Wang,and Zhiren Lin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eValidation: Shengmin Chen, Guoping Wang,and Zhiren Lin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eVisualization: Shengmin Chen, Guoping Wang,and Zhiren Lin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; original draft: Shengmin Chen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; review and editing:Feng Yuan.\u003c/p\u003e\u003cp\u003eData Access Statement:\u0026nbsp;The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eConflict of Interest Declaration: Written informed consent for participation was not required for this study, in accordance with national legislation and institutional requirements. The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSharmistha Sarkar,Christopher A.Bristow,Prasenjit Dey,et al.PRKCI promotes immune suppression in ovarian cancer[J].GENES\u0026amp;DEVELOPMENT,2017,31:1109\u0026ndash;1121.doi:10.1101/gad.296640.117.[PubMed]\u003c/li\u003e\n\u003cli\u003eCHEN Shengmin, WANG Guoping, LIN Zhiren, et al. Expression of PKC\u0026iota;/YAP1 in Cervical Cancer and Its Clinical Significance[J]. Zhong Liu Fang Zhi Yan Jiu, 2021, 48(10): 970-973.[CrossRef]\u003c/li\u003e\n\u003cli\u003eSichero,Laura,Rollison,Dana E,Amorrortu,Rossybelle P,et al.Beta Human Papillomavirus and Associated Diseases[J].Acta Cytologica,2019:1-9.doi:10.1159/000492659.[PubMed]\u003c/li\u003e\n\u003cli\u003eGilkey,Melisa B,Margolis,Marjorie A.Human Papillomavirus Vaccination Coverage Gaps in Young Adolescents[J].The Journal of Infectious Diseases,2019:727-729.doi:10.1093/infdis/jiy683.[PubMed]\u003c/li\u003e\n\u003cli\u003eHanbazazh Mehenaz,Gyure Kymberly A.Ocular Human Papillomavirus Infections[J].Archives of Pathology\u0026amp;Laboratory Medicine,2018:706-710.doi:10.5858/arpa.2017-0571-RA.[PubMed]\u003c/li\u003e\n\u003cli\u003eKawano T, Inokuchi J, Eto M, Murata M, Kang JH. Activators and Inhibitors of Protein Kinase C (PKC): Their Applications in Clinical Trials. Pharmaceutics. 2021 Oct 20;13(11):1748. doi: 10.3390/pharmaceutics13111748. [PubMed]\u003c/li\u003e\n\u003cli\u003eUbba V, Gupta RK, Hakim BA, Bora HK, Sachdev M, Tripathi R, Jha RK. PKC-\u0026beta;II is downregulated in the premature ovarian failure SD rat model. Reprod Biol. 2023 Jun;23(2):100754. doi: 10.1016/j.repbio.2023.100754.[PubMed]\u003c/li\u003e\n\u003cli\u003eHarden,Mallory E,Munger,Karl.HUMAN PAPILLOMAVIRUS MOLECULAR BIOLOGY[J].Mutation Research/Reviews in Mutation Research,2016:S1383574216300679.doi:10.1016/j.mrrev.2016.07.002.[PubMed]\u003c/li\u003e\n\u003cli\u003eSchiffman,Mark,Doorbar,John,Wentzensen,Nicolas,et al.Carcinogenic human papillomavirus infection[J].Nature Reviews Disease Primers,2016:16086.doi:10.1038/nrdp.2016.86.[PubMed]\u003c/li\u003e\n\u003cli\u003ePearsall,Elizabeth A.Connor,Kip M.Atypical Protein Kinase C[J].The American Journal of Pathology,2018:2142-2146.doi:10.1016/j.ajpath.2018.07.006.[PubMed]\u003c/li\u003e\n\u003cli\u003eParker,Peter J,Justilien,Verline,Riou,et al.Atypical Protein Kinase C\u0026iota; as a human oncogene and therapeutic target[J].Biochemical Pharmacology,2014:1-11.doi:10.1016/j.bcp.2013.10.023.[PubMed]\u003c/li\u003e\n\u003cli\u003eParker PJ, Justilien V, Riou P, Linch M, Fields AP. Atypical protein kinase C\u0026iota; as a human oncogene and therapeutic target[J]. Biochem Pharmacol. 2014 Mar 1;88(1):1-11. doi: 10.1016/j.bcp.2013.10.023.[PubMed]\u003c/li\u003e\n\u003cli\u003eQiu S, Zhang K, Chen S, Yin S. Circular RNA PRKCI (hsa_circ_0067934): a potential target in the pathogenesis of human malignancies. Front Oncol. 2024 Apr 29;14:1365032. doi: 10.3389/fonc.2024.1365032.[PubMed]\u003c/li\u003e\n\u003cli\u003eFields AP, Ali SA, Murray NR. Oncogenic PKC\u0026iota; decides tumor-initiating cell fate. Cell Cycle. 2016 Sep 16;15(18):2383-4. doi: 10.1080/15384101.2016.1194624.[PubMed]\u003c/li\u003e\n\u003cli\u003eWu Z, Huang C, Li R, Li H, Lu H, Lin Z. PRKCI Mediates Radiosensitivity via the Hedgehog/GLI1 Pathway in Cervical Cancer. Front Oncol. 2022 Jun 16;12:887139. doi: 10.3389/fonc.2022.887139.[PubMed]\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cervical carcinomalesions, protein kinase Cι, yes associated protein 1, human papillomavirus, T cells","lastPublishedDoi":"10.21203/rs.3.rs-5663204/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5663204/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eTo explore the role of Protein Kinase Cι(PKCι/PRKCI) in yes-associated protein 1 (YAP1) \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003esignaling in cervical cancer and its relationship with prognosis.\u003c/span\u003eSelect normal cervical tissue(NCT)low-grade squamous intraepithelial lesions(LSIL),high-grade squamous intraepithelial lesions(HSIL)and cervical squamous cell carcinoma(SCC)in 80 cases each.PKCι and YAP1 were analyzed by immunohistochemistry(IHC)and analyzed for correlation,clinical pathology and prognosis.Cervical cancer SiHa cell lines were transfected with PKCι gene overexpression,transfection efficiency was evaluated by inverted fluorescence microscope,viability was treated with PKCι inhibitor aurothiomalate,which was measured by CCK-8,and cell migration was measured by transwell experiments.The PKCι gene expression was measured by real-time reverse transcription polymerase chain reaction(qRT-PCR)and verified by transcriptome sequencing and qRT-PCR. \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eThe positivity rates for PKC\u003c/span\u003eι and YAP1 varied in \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003epatients with\u003c/span\u003e NCT,LSIL, and HSIL (\u003cspan type=\"ItalicSmallCaps\" class=\"ItalicSmallCaps\" name=\"Emphasis\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eBoth PKC\u003c/span\u003eι \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eand YAP1 expression showed statistically significant differences between different degrees\u003c/span\u003e of SCC \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003edifferentiation and the presence of vasculoma plugs(\u003c/span\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eUnivariate analysis\u003c/span\u003e of \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ethe survival prognosis of patients with SCC showed that protein expression,differentiation,lymph node metastasis, and vasoma metastasis were independent factors affecting overall survival(\u003c/span\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eThe expression level of PKC\u003c/span\u003eι transfected PKCι mRNA in SiHa cells was significantly higher than that in empty-loaded liposomes(\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePatients with cervical lesions are often accompanied by abnormal expression of PKC\u003c/span\u003eι and YAP1,which may have synergistic effects between each other to affect the occurrence and development of SCC and its prognosis,promote the proliferation and migration of SCC cells,and provide a possible basis for the pathogenesis study of SCC and its diagnosis and treatment to determine the prognosis.\u003c/p\u003e","manuscriptTitle":"The role of pkcι in yap 1 signaling in cervical cancer and its relationship with prognosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-24 17:29:06","doi":"10.21203/rs.3.rs-5663204/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7511ff77-aa9c-4627-94d5-9e59676ae4e9","owner":[],"postedDate":"December 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-29T02:53:10+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-24 17:29:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5663204","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5663204","identity":"rs-5663204","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}