Correlation analysis of Helicobacter pylori infection, p-STAT3 with colon cancer and precancerous lesions

Correlation analysis of Helicobacter pylori infection, p-STAT3 with colon cancer and precancerous lesions | 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 Correlation analysis of Helicobacter pylori infection, p-STAT3 with colon cancer and precancerous lesions Zhongsen Dou, Lingrun Ye, Fanglai Zhu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6554594/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Background This study aimed to investigate the correlations among Helicobacter pylori (Hp) infection, p-STAT3, colon cancer and precancerous lesions. Methods A total of 124 patients who underwent colonoscopy at the Endoscopy Center of Anqing First People's Hospital from January 2021 to June 2024 were enrolled. According to the pathological results of colonoscopy, the patients were divided into four groups: the adenoma group, the high-grade group, the cancer group and the control group. The expression of p-STAT3 and the status of Hp infection in each group were mainly observed. Results In Helicobacter pylori (Hp) infection, significant differences were observed between the high-grade group (71.0%), the cancer group (71.0%), and the control group (25.8%) (P < 0.05). Additionally, there were significant differences between the high-grade group (71.0%), the cancer group (71.0%), and the adenoma group (29.0%) in Hp infection (P < 0.05). Regarding the positive expression of p-STAT3, significant differences were found between the high-grade group (64.5%), the cancer group (74.2%), and the control group (12.9%) (P < 0.05). Moreover, significant differences existed between the high-grade group (64.5%), the cancer group (74.2%), and the adenoma group (29.0%) in the positive expression of p-STAT3 (P < 0.05). Spearman correlation analysis was used to examine the relationship between Hp infection and p-STAT3, revealing a positive correlation between Hp positivity (%) and p-STAT3 positivity (%) (rs = 0.209, P = 0.02). Multivariate Logistic regression analysis indicated that Hp infection and p-STAT3 positivity were independent risk factors for the cancer group with statistical significance (P < 0.05), and they were also independent risk factors for the high-grade group with statistical significance (P < 0.05). Conclusion Helicobacter pylori (Hp) infection and increased expression of p-STAT3 increase the risk of colorectal cancer and colorectal adenoma with high-grade dysplasia and are independent risk factors for both. There is a positive correlation between Hp infection and upregulated p-STAT3 expression in patients, suggesting that the two may jointly participate in the occurrence and development of colorectal cancer and precancerous lesions. Helicobacter pylori infection p-STAT3 Colorectal cancer Precancerous lesions Correlation Figures Figure 1 Background Colorectal cancer (CRC) ranks as the third most common malignancy globally, posing a serious threat to human health [ 1 ] . In China, with the changes in lifestyle and dietary habits, the incidence of colorectal cancer has been on the rise [ 2 ] . Despite advances in screening programs, less than half of cancer cases are diagnosed at the locally advanced stage, underscoring the urgent need for novel biomarkers targeting precancerous lesions [ 3 ] .Helicobacter pylori (Hp) infection is the most common bacterial infection worldwide and is closely related to the occurrence and development of various gastrointestinal diseases [ 4 ] , p-STAT3 (phosphorylated signal transducer and activator of transcription 3) is the activated form of STAT3, which is involved in multiple biological processes such as cell proliferation, differentiation, and apoptosis [ 5 ] . In recent years, studies have found that Hp infection, p-STAT3 are closely related to the occurrence and development of colorectal cancer and precancerous lesions. This study explored the correlation among Hp infection, p-STAT3, colorectal cancer, and precancerous lesions, providing new ideas for the clinical prevention and treatment of colorectal cancer. Methods Study Design and Participants A total of 124 patients who underwent both gastroscopy and colonoscopy and pathological biopsy at the Endoscopy Center of Anqing First People's Hospital from January 2021 to June 2024 were selected. According to the colonoscopy pathological examination results, they were divided into 4 groups: the adenoma group (colorectal adenoma), the high - grade group (colorectal adenoma with high - grade dysplasia), the cancer group (colorectal cancer), and the control group (patients with normal colonoscopy pathological diagnosis). Inclusion criteria: (1) Patients who completed gastroscopy and colonoscopy; (2) Detection of Helicobacter pylori by gastroscopic biopsy; (3) Patients who had never received standardized Helicobacter pylori eradication treatment and had no history of acid - suppressing drugs, antibiotics, or traditional Chinese medicines with antibacterial effects within at least 4 weeks. Exclusion criteria: (1) Age < 18 years; (2) Inadequate bowel preparation or inability to complete total colonoscopy; (3) Patients pathologically confirmed with inflammatory bowel disease, ischemic enteritis, or non - specific enteritis; (4) Patients with a history of familial adenomatous polyposis, inflammatory bowel disease, or colorectal resection; (5) Patients with recent acute infectious diseases; (6) Cases treated with radiotherapy, chemotherapy, or traditional Chinese medicine were excluded. All patients undergoing gastroscopy and colonoscopy signed the informed consent form for gastroscopy and colonoscopy. This study was approved by the Medical Ethics Committee of Anqing First People's Hospital. Immunohistochemistry Patients meeting the criteria were divided into 4 groups. Before the examination in each group, nurses instructed the patients to take Compound Polyethylene Glycol Electrolyte Powder for Bowel Cleansing (Polyethylene Glycol Electrolyte Powder 4000, 10*15 sachets, Chongqing Huasen Pharmaceutical Co., Ltd.), with the standard of excreting clear watery stools. Both gastroscopy and colonoscopy were performed by 3 professional digestive endoscopists in our hospital with over 10 years of work experience, with reaching the ileocecal region as the standard. Intestinal pathological examination and immunohistochemical detection of p - STAT3 were carried out; tissue sections were sent for Helicobacter pylori examination during gastroscopy. Main Reagents and Instruments Main reagents 1. Anti-STAT3 (phospho Y705) antibody [EPR23968-52], Abcam (Shanghai) 2. DAB Chromogenic Kit, CST Biological Company (USA) 3. Immunohistochemistry kit, Abcam (Shanghai) 4. Citric acid antigen retrieval buffer, Maixin Biotechnology Development Co., Ltd. (Fuzhou) 5. PBS buffer, Baikaimei Biotechnology Co., Ltd. (Shenzhen) 6.30% H₂O₂, Guangdong Xilong Scientific Co., Ltd. Ready-to-use normal goat serum, Melone Biotechnology (Dalian) Goat anti-rabbit IgG-HRP, Boster Biological Technology (Beijing) Main Instruments 1. Paraffin microtome, Leica (Germany) 2. Slide spreading and baking machine, Thermo Fisher Scientific (USA) 3. OLYMPUS BX43 microscope, Olympus Corporation (Japan) 4. Slide scanning and analysis system, 3DHistech (Hungary) 5. OLYMPUS CV-290 Electronic Gastrointestinal Endoscope System, Olympus Corporation (Japan) 6. OLYMPUS CF-H290I colonoscope, Olympus Corporation (Japan) 7. OLYMPUS GIF-Q260J gastroscope, Olympus Corporation (Japan) Immunohistochemical staining The collected tissue samples were placed in fixative for fixation, embedded in paraffin and then sectioned. After dewaxing, the sections were hydrated through gradient ethanol. The sections were immersed in the retrieval solution and heated for antigen retrieval. After the solution cooled down to room temperature, the sections were soaked in PBS buffer. Then, they were taken out and the excess liquid was wiped off with a clean gauze. An endogenous peroxidase blocker was added to the sectioned tissue. After washing with water, the primary antibody (p-STAT3 antibody) was added drop - by - drop and incubated overnight, followed by the addition of the secondary antibody. After DAB color development, the sections were differentiated with a differentiating solution and then turned blue. They were dehydrated and cleared. After the sections were air - dried, they were mounted, and the slides were read and interpreted under a microscope. Interpretation of immunohistochemical staining results The positive products of p-STAT3 protein immunohistochemistry appear brownish-yellow or brownish-brown, mainly located in the nucleus. The results were interpreted blindly by two experienced pathologists using a semi-quantitative comprehensive scoring method: Four fields were randomly selected under a high-power microscope, and the grades were divided according to the positive staining intensity and positive area. Positive intensity: 0 points for basically no staining, 1 point for light yellow, 2 points for brownish-yellow, and 3 points for brownish-brown. Positive area: 0 points for ≤ 10%, 1 point for > 10% − 25%, 2 points for > 25% − 50%, and 3 points for > 50%. The total staining score is the product of the intensity score and the positive area score. A score of ≤ 3 is considered negative, and a score of ≥ 4 is considered positive. Statistical Analysis All data were entered using Excel and statistically analyzed using SPSS 27. Quantitative data were presented as mean ± standard deviation (x ± s), while categorical data were presented as the number of cases (percentage). Independent sample t - test was used for comparison between two groups of quantitative data, and Mann - Whitney U test was used for non - normal quantitative data. ANOVA was used for comparison among multiple groups, LSD - t test was used for pairwise comparison, and Kruskal - Wallis H test was used for non - normal quantitative data. Chi - square test was used for comparison of categorical data. Spearman correlation analysis was used to analyze the relationship between Helicobacter pylori infection and p - STAT3. Multivariate Logistic regression analysis was applied for multivariate analysis. A P - value < 0.05 was considered statistically significant for all statistical methods. Results Baseline Characteristics Comparison of baseline data among the four groupsAccording to the inclusion and exclusion criteria, a total of 124 patients were enrolled, including: 31 cases in the cancer group, with 22 males and 9 females, aged 51–79 (62.32 ± 7.52) years; 31 cases in the high - grade group, with 23 males and 8 females, aged 52–77 (62.0 ± 7.43) years; 31 cases in the adenoma group, with 20 males and 11 females, aged 53–78 (60.74 ± 6.06) years; 31 cases in the control group, with 18 males and 13 females, aged 53–71 (59.35 ± 4.68) years. Comparison of the general data among the four groups showed that there were no statistically significant differences in gender, age, smoking history, drinking history, history of hypertension, history of diabetes and history of hyperuricemia among the four groups of patients (P > 0.05). See Table 1 . Table 1 Comparison of general data among the four groups control group Adenoma group High-level segment Cancer group x 2 /F/H P value n 31 31 31 31 Gender (male/female) 18/13 20/11 23/8 22/9 2.15 0.542 Age (years) 59.35 ± 4.68 60.74 ± 6.07 62.19 ± 7.44 62.32 ± 7.53 1.418 0.241 smoke(%) 5(16.1) 8(25.8) 7(22.6) 5(16.1) 1.353 0.717 alcoholic consumption (%) 4(12.9) 6(19.4) 6(19.4) 8(25.8) 1.653 0.647 hypertension(%) 7(22.6) 11(35.5) 9(29.0) 15(48.4) 5.041 0.169 diabetes mellitus(%) 3(9.7) 7(22.6) 7(22.6) 6(19.4) 2.295 0.513 hyperuricemia (%) 4(12.9) 3(9.7) 7(22.6) 3(9.7) 2.931 0.402 Hp Infection and p-STAT3 Expression The patients were classified by pathology to analyze the relationship between Helicobacter pylori infection, p-STAT3 positive and different colorectal lesions. The results showed that among H. pylori infections, the high-grade group (71.0%), cancer group (71.0%) vs control group (25.8%) statistically significant (P < 0.05); high-level group (71.0%), cancer group (71.0%) and adenoma group (29.0%), the difference was statistically significant (P < 0.05); among p-STAT3 positive, the difference was statistically significant (P < 0.05) between high-grade group (64.5%), cancer group (74.2%) and control group (12.9%); the difference was statistically significant (P < 0.05) between high-grade group (64.5%), cancer group (74.2%) and adenoma group (29.0%); see Table 2 . Table 2 Comparison of Helicobacter pylori infection and p-STAT3 positive in different colorectal diseases control group Adenoma group High-level segment Cancer group x 2 P value n 31 31 31 31 Hp positive(%) 8(25.8) 9(29.0) 22(71.0) ab 22(71) ab 23.587 <0.001 p-STAT3 positive(%) 4(12.9) 9(29.0) 20(64.5) ab 23(74.2) ab 31.521 <0.001 Note: a indicates comparison with control group, P < 0.05; b indicates comparison with adenoma group, P < 0.05. Correlation analysis between Helicobacter pylori infection and p-STAT3 Spearman correlation analysis was used to examine the relationship between Helicobacter pylori infection and p-STAT3. According to our data, there was a positive correlation between Hp positivity (%) and p-STAT3 positivity (%) (rs = 0.209, P = 0.02), as shown in Table 3 . Table 3 Correlation analysis between Helicobacter pylori infection and p-STAT3 factor Hp positive(%) p-STAT3 positive(%) Rs value P value Rs value P value Hp positive(%) 1 - 0.209 0.02 p-STAT3 positive(%) 0.209 0.02 1 - Correlation and Risk Factors In the statistical analysis, factors with significant differences (P < 0.05) such as HP infection and p - STAT3 were used as independent variables, and the occurrence of colorectal adenoma, high - grade lesions, and cancer were used as dependent variables for multivariate Logistic regression analysis to explore the independent risk factors for colorectal adenoma, colorectal high - grade lesions, and colorectal cancer. The results showed that HP infection and positive p - STAT3 were statistically significant independent risk factors for the colorectal cancer group (P < 0.05), and HP infection and positive p - STAT3 were statistically significant independent risk factors for the colorectal high - grade lesion group (P < 0.05), as shown in Table 4 . Table 4 Logistic regression analysis of Hp and p - STAT3 in the adenoma group, high - grade group, and cancer group factor B value SE value Waldx 2 value P value OR value 95%CI Adenoma group Hp 0.168 0.575 0.085 0.770 1.183 0.383–3.650 p-STAT3 1.017 0.666 2.330 0.127 2.765 0.749–10.203 High-level segment hp 1.968 0.619 10.093 0.001 7.155 2.125–24.092 p-STAT3 2.523 0.688 13.450 <0.001 12.468 3.237–48.018 Cancer group hp 1.971 0.638 9.539 0.002 7.179 2.055–25.080 p-STAT3 2.981 0.708 17.736 <0.001 19.715 4.923–78.958 Discussion The occurrence and development of colorectal cancer (CRC) is a complex, multi - stage and multi - factor - involved process, which encompasses multiple levels such as gene mutations, epigenetic alterations, and dysregulation of the microenvironment. The pathological evolution generally progresses from normal mucosa to abnormal hyperplasia and then to cancer. Colorectal adenoma with high - grade dysplasia is usually characterized by abnormal cell cycle regulation and significant atypia, but the basement membrane remains intact. We define this lesion as a precancerous lesion. Colorectal cancer originates from the epithelial cells of the colorectal mucosa and consists of cells and/or structures with malignant morphological features that penetrate the muscularis mucosa and infiltrate the submucosa or deeper layers.This study found that the Helicobacter pylori (Hp) infection rate was significantly higher in patients with colorectal adenoma with high - grade dysplasia or colorectal cancer than in those with colorectal adenoma or in normal individuals (P < 0.05). Additionally, the positive expression rate of p - STAT3 in the pathological specimens was significantly higher in patients with colorectal adenoma with high - grade dysplasia or colorectal cancer than in those with colorectal adenoma or in normal individuals (P < 0.05). Spearman's correlation analysis was used to examine the relationship between Hp infection and p - STAT3 expression, and a positive correlation was found between the percentage of Hp - positive cases and the percentage of p - STAT3 - positive cases (rs = 0.209, P = 0.02).Multivariate Logistic regression analysis showed that Helicobacter pylori (Hp) infection and positive p-STAT3 were independent risk factors for colorectal cancer and colorectal adenoma with high-grade dysplasia, which was statistically significant (P < 0.05). The results of this study were highly consistent with recent large-scale population studies. Boustany et al. [ 6 ] based on a cohort study of 47.71 million people, found that a history of Hp infection was significantly associated with the risk of colorectal cancer (OR = 1.89), suggesting that Hp may promote carcinogenesis through direct or indirect mechanisms. A meta-analysis of the East Asian population showed that the association strength between Hp infection and colorectal cancer (OR = 1.72) was higher than the global average [ 7 ] , which may be related to the virulence of region-specific strains or the host's genetic background. In addition, a systematic review by Liu et al. [ 8 ] indicated that Hp infection significantly increased the risk of colorectal adenoma (OR = 1.67), especially high-grade dysplasia, supporting its role in the early stage of the "adenoma-carcinoma" sequence. Potential mechanisms of Hp infection activating the STAT3 pathway: (1) Chronic inflammation and cytokine release. Hp infection can induce chronic inflammation in the gastric mucosa and intestinal epithelium, promoting the secretion of pro-inflammatory factors (such as IL-6) [ 9 ] . These cytokines activate JAK2 kinase by binding to cell membrane receptors, then phosphorylate STAT3 (p-STAT3) and promote its entry into the nucleus to regulate the transcription of target genes. In colorectal cancer, the IL-6/JAK2/STAT3 axis has been confirmed to promote cell proliferation and inhibit apoptosis [ 10 ] .(2) Direct effects of Hp virulence factors (such as cytotoxin-associated protein A). After being injected into host cells via the type IV secretion system, cytotoxin-associated gene A (CagA) can activate tyrosine family kinases [ 11 ] , directly phosphorylate STAT3 independently of cytokine signals. Additionally, CagA can upregulate the expression of COX-2 [ 12 ] , promote the synthesis of prostaglandin E2 (PGE2), and further activate the STAT3 pathway.(3) Epigenetic regulation. Hp infection induces the silencing of miR490-3p. The downregulation of miR490-3p leads to an increase in the expression of DARPP-32. The elevated level of DARPP-32 protein triggers the continuous activation of the PI3K/AKT and STAT3 signaling pathways, specifically manifested as an increase in the levels of phosphorylated AKT (p-AKT) and phosphorylated STAT3 (p-STAT3) [ 13 ] .Pro-tumorigenic effects of the STAT3 pathway in colorectal cancer: (1) Anti-apoptosis: p-STAT3 upregulates anti-apoptotic proteins such as Bcl-2 and inhibits cell apoptosis [ 14 ] . (2) Proliferation promotion: It activates genes such as Cyclin D1 and c-Myc to drive cell cycle progression [ 15 ] . (3) Immune escape: It induces the expression of PD-L1, inhibits T cell activity, and promotes immune suppression in the tumor microenvironment [ 16 ] . This study found that Helicobacter pylori (Hp) infection and increased expression of p-STAT3 increased the risk of colorectal cancer (CRC) and colorectal adenoma with high-grade dysplasia, and were independent risk factors for both. There was a positive correlation between Hp infection and upregulated p-STAT3 expression in patients, suggesting that they may jointly participate in the occurrence and development of CRC and precancerous lesions. The occurrence and development of CRC are the result of the combined action of genes, environment, and microbiome. The average period from adenoma to carcinogenesis is about 10–15 years. This finding provides new ideas for the early screening of high-risk populations for CRC. In addition, eradicating Hp infection or blocking the p-STAT3 pathway may become a new strategy for preventing or treating CRC, especially in areas with a high prevalence of Hp. Limitations and recommendations: (1) The single-center design and small sample size may affect the universality of the results; (2) The upstream regulatory factors of STAT3 (such as IL-6 and JAK2) were not detected, which limited the depth of mechanism exploration. Future studies need to conduct multi-center, large-sample cohort validation. Moreover, exploring the predictive value of p-STAT3 expression combined with Hp infection status for the response to chemotherapy or immunotherapy will have important clinical significance. In conclusion,Helicobacter pylori (Hp) infection and increased expression of p-STAT3 increase the risk of colorectal cancer and colorectal adenoma with high-grade dysplasia and are independent risk factors for both. There is a positive correlation between Hp infection and upregulated p-STAT3 expression in patients, suggesting that the two may jointly participate in the occurrence and development of colorectal cancer and precancerous lesions. Abbreviations CRC Colorectal cancer HP Helicobacter pylori p-STAT3 phosphorylated signal transducer and activator of transcription 3 Declarations Acknowledgements None Author contributions Conceptualization:Zhongsen Dou Fanglai Zhu. Funding acquisition: Fanglai Zhu. Investigation: Zhongsen Dou Methodology:Zhongsen Dou,Lingrun Ye Resources: Fanglai Zhu,Zhongsen Dou Supervision: Fanglai Zhu ,Lingrun Ye Writing – original draft: Zhongsen Dou Writing – review & editing: Fanglai Zhu. Authors' contributions FLZ conceptualized the case report and did the procedure. ZSDand LRY prepared the initial drafting of the paper. ZSD and FLZ did the research, editing and final drafting of the paper. ZSD and FL Z contributed equally.All authors read and approved the final manuscript. Ethics approval and consent to participate This subject has been approved by the ethics committee of Anqing first people's hospital. Written informed consent was obtained. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to concealtheir identity, but anonymity cannot be guaranteed. Funding Nil. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Author details The first author Zhongsen Dou：2023 graduate student of gastroenterology department ，Wannan Medical College，Wuhu，Anhui，China( e-mail: [email protected] ）； The second author Lingrun Ye:2022 graduate student of gastroenterology department ，Wannan Medical College，Wuhu，Anhui，China(e-mail: [email protected] ）； * Correspondence: Fanglai Zhu, Department of Gastroenterology, Anqing First People’s Hospital , Anqing 246000, China (e-mail: [email protected] ). References Morgan E, Arnold M, Gini A, Gut et al. 2023;72(2):338–44. Xu L, Zhao J, Li Z, et al. National and subnational incidence, mortality and associated factors of colorectal cancer in China: A systematic analysis and modelling study. J Glob Health. 2023;13:04096. Zygulska AL, Pierzchalski P. Novel Diagnostic Biomarkers in Colorectal Cancer. Int J Mol Sci. 2022;23(2):852. Malfertheiner P, Camargo MC, El-Omar E, et al. Helicobacter pylori infection. Nat Rev Dis Primers. 2023;9(1):19. Sun Y, Gong W, Zhang S. METTL3 promotes colorectal cancer progression through activating JAK1/STAT3 signaling pathway. Cell Death Dis. 2023;14(11):765. Boustany A, Onwuzo S, Almomani A, Asaad I. Epidemiology and risk of colorectal cancer in patients with a history of Helicobacter pylori infection: a population-based study. Ann Gastroenterol. 2023;36(2):203–7. Ma L, Guo W, Zeng Z, Yang F, Tang S, Ling Y. Colorectal cancer risk in East Asian patients with Helicobacter pylori infection: A systematic review and meta-analysis. Med (Baltim). 2023;102(10):e33177. Liu Y, Yang DQ, Jiang JN, Jiao Y. Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer. World J Gastrointest Surg. 2024;16(4):1008–16. Guo Y, Ding S. Helicobacter pylori Thioredoxin1 May Play a Highly Pathogenic Role via the IL6/STAT3 Pathway. Gastroenterol Res Pract. 2022;2022:3175935. Huang B, Lang X, Li X. The role of IL-6/JAK2/STAT3 signaling pathway in cancers. Front Oncol. 2022;12:1023177. Zhang X, Soutto M, Chen Z et al. Induction of Fibroblast Growth Factor Receptor 4 by Helicobacter pylori via Signal Transducer and Activator of Transcription 3 With a Feedforward Activation Loop Involving SRC Signaling in Gastric Cancer [published correction appears in Gastroenterology. 2023;165(1):306. doi: 10.1053/j.gastro.2023.05.004.]. Gastroenterology. 2022;163(3):620–636.e9. Sakatani A, Hayashi Y, Saiki H, et al. A novel role for Helicobacter pylori cytotoxin-associated gene A in negative regulation of autophagy in human gastric cells. BMC Gastroenterol. 2023;23(1):326. Zhu S, Khalafi S, Chen Z, et al. Silencing of miR490-3p by H. pylori activates DARPP-32 and induces resistance to gefitinib. Cancer Lett. 2020;491:87–96. Hsieh YC, Dai YC, Cheng KT, et al. Blockade of the SRC/STAT3/BCL-2 Signaling Axis Sustains the Cytotoxicity in Human Colorectal Cancer Cell Lines Induced by Dehydroxyhispolon Methyl Ether. Biomedicines. 2023;11(9):2530. Ning R, Chen G, Fang R, Zhang Y, Zhao W, Qian F. Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells. Biol Res. 2021;54(1):40. Liu C, Yao Z, Wang J, et al. Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway [published correction appears in. Cell Death Differ. 2020;27(7):2293. Additional Declarations No competing interests reported. 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16:38:12","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":85127,"visible":true,"origin":"","legend":"","description":"","filename":"b0d5064f541a4dfba5c6d624e56397c41structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-6554594/v1/6667645574899a58490b4e25.xml"},{"id":93062860,"identity":"76cecd33-8cbe-4b3f-93c5-2c6b0e58ce68","added_by":"auto","created_at":"2025-10-08 16:38:04","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92112,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-6554594/v1/1d8ce7057d5f29b1f8b81731.html"},{"id":93063430,"identity":"ef56c9a9-191f-402e-a106-43fc5d2ad585","added_by":"auto","created_at":"2025-10-08 16:38:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":652394,"visible":true,"origin":"","legend":"\u003cp\u003eUnnumbered image in the\u003cstrong\u003e \u003c/strong\u003emethod of section\u003c/p\u003e\n\u003cp\u003eSTAT3 showed negative expression in normal mucosal tissues (A) (B), and strongly positive expression in (C) (D) (positive granules were located in the cell nucleus) (SP×200)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6554594/v1/7bda2c6764e7a710a186bbb6.png"},{"id":93064369,"identity":"a68d9b37-69a6-47cb-8c91-6b57f250e468","added_by":"auto","created_at":"2025-10-08 16:41:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1404415,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6554594/v1/511fb310-3186-48a0-9775-a9696276942b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlation analysis of Helicobacter pylori infection, p-STAT3 with colon cancer and precancerous lesions","fulltext":[{"header":"Background","content":"\u003cp\u003eColorectal cancer (CRC) ranks as the third most common malignancy globally, posing a serious threat to human health \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e. In China, with the changes in lifestyle and dietary habits, the incidence of colorectal cancer has been on the rise\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. Despite advances in screening programs, less than half of cancer cases are diagnosed at the locally advanced stage, underscoring the urgent need for novel biomarkers targeting precancerous lesions\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e.Helicobacter pylori (Hp) infection is the most common bacterial infection worldwide and is closely related to the occurrence and development of various gastrointestinal diseases\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e, p-STAT3 (phosphorylated signal transducer and activator of transcription 3) is the activated form of STAT3, which is involved in multiple biological processes such as cell proliferation, differentiation, and apoptosis\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. In recent years, studies have found that Hp infection, p-STAT3 are closely related to the occurrence and development of colorectal cancer and precancerous lesions. This study explored the correlation among Hp infection, p-STAT3, colorectal cancer, and precancerous lesions, providing new ideas for the clinical prevention and treatment of colorectal cancer.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Design and Participants\u003c/h2\u003e\n \u003cp\u003eA total of 124 patients who underwent both gastroscopy and colonoscopy and pathological biopsy at the Endoscopy Center of Anqing First People\u0026apos;s Hospital from January 2021 to June 2024 were selected. According to the colonoscopy pathological examination results, they were divided into 4 groups: the adenoma group (colorectal adenoma), the high - grade group (colorectal adenoma with high - grade dysplasia), the cancer group (colorectal cancer), and the control group (patients with normal colonoscopy pathological diagnosis). Inclusion criteria: (1) Patients who completed gastroscopy and colonoscopy; (2) Detection of Helicobacter pylori by gastroscopic biopsy; (3) Patients who had never received standardized Helicobacter pylori eradication treatment and had no history of acid - suppressing drugs, antibiotics, or traditional Chinese medicines with antibacterial effects within at least 4 weeks. Exclusion criteria: (1) Age\u0026thinsp;\u0026lt;\u0026thinsp;18 years; (2) Inadequate bowel preparation or inability to complete total colonoscopy; (3) Patients pathologically confirmed with inflammatory bowel disease, ischemic enteritis, or non - specific enteritis; (4) Patients with a history of familial adenomatous polyposis, inflammatory bowel disease, or colorectal resection; (5) Patients with recent acute infectious diseases; (6) Cases treated with radiotherapy, chemotherapy, or traditional Chinese medicine were excluded. All patients undergoing gastroscopy and colonoscopy signed the informed consent form for gastroscopy and colonoscopy. This study was approved by the Medical Ethics Committee of Anqing First People\u0026apos;s Hospital.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eImmunohistochemistry\u003c/h3\u003e\n\u003cp\u003ePatients meeting the criteria were divided into 4 groups. Before the examination in each group, nurses instructed the patients to take Compound Polyethylene Glycol Electrolyte Powder for Bowel Cleansing (Polyethylene Glycol Electrolyte Powder 4000, 10*15 sachets, Chongqing Huasen Pharmaceutical Co., Ltd.), with the standard of excreting clear watery stools. Both gastroscopy and colonoscopy were performed by 3 professional digestive endoscopists in our hospital with over 10 years of work experience, with reaching the ileocecal region as the standard. Intestinal pathological examination and immunohistochemical detection of p - STAT3 were carried out; tissue sections were sent for Helicobacter pylori examination during gastroscopy.\u003c/p\u003e\n\u003ch3\u003eMain Reagents and Instruments\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003eMain reagents\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e1. Anti-STAT3 (phospho Y705) antibody [EPR23968-52], Abcam (Shanghai)\u003c/p\u003e\u003cspan\u003e2. DAB Chromogenic Kit, CST Biological Company (USA)\u003cbr\u003e\u003c/span\u003e\u003cspan\u003e\n \u003cp\u003e3. Immunohistochemistry kit, Abcam (Shanghai)\u003c/p\u003e\n\u003c/span\u003e\u003cspan\u003e\n \u003cp\u003e4. Citric acid antigen retrieval buffer, Maixin Biotechnology Development Co., Ltd. (Fuzhou)\u003c/p\u003e\n\u003c/span\u003e\u003cspan\u003e\n \u003cp\u003e5. PBS buffer, Baikaimei Biotechnology Co., Ltd. (Shenzhen)\u003c/p\u003e\n\u003c/span\u003e\u003cspan\u003e\n \u003cp\u003e6.30% H₂O₂, Guangdong Xilong Scientific Co., Ltd.\u003c/p\u003e\n\u003c/span\u003e\u003cspan\u003e\n \u003cp\u003eReady-to-use normal goat serum, Melone Biotechnology (Dalian)\u003c/p\u003e\n\u003c/span\u003e\u003cspan\u003e\n \u003cp\u003eGoat anti-rabbit IgG-HRP, Boster Biological Technology (Beijing)\u003c/p\u003e\n\u003c/span\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMain Instruments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1. Paraffin microtome, Leica (Germany)\u003c/p\u003e\n\u003cp\u003e2. Slide spreading and baking machine, Thermo Fisher Scientific (USA)\u003c/p\u003e\n\u003cp\u003e3. OLYMPUS BX43 microscope, Olympus Corporation (Japan)\u003c/p\u003e\n\u003cp\u003e4. Slide scanning and analysis system, 3DHistech (Hungary)\u003c/p\u003e\n\u003cp\u003e5. OLYMPUS CV-290 Electronic Gastrointestinal Endoscope System, Olympus Corporation (Japan)\u003c/p\u003e\n\u003cp\u003e6. OLYMPUS CF-H290I colonoscope, Olympus Corporation (Japan)\u003c/p\u003e\n\u003cp\u003e7. OLYMPUS GIF-Q260J gastroscope, Olympus Corporation (Japan)\u003c/p\u003e\n\u003ch3\u003eImmunohistochemical staining\u003c/h3\u003e\n\u003cp\u003eThe collected tissue samples were placed in fixative for fixation, embedded in paraffin and then sectioned. After dewaxing, the sections were hydrated through gradient ethanol. The sections were immersed in the retrieval solution and heated for antigen retrieval. After the solution cooled down to room temperature, the sections were soaked in PBS buffer. Then, they were taken out and the excess liquid was wiped off with a clean gauze. An endogenous peroxidase blocker was added to the sectioned tissue. After washing with water, the primary antibody (p-STAT3 antibody) was added drop - by - drop and incubated overnight, followed by the addition of the secondary antibody. After DAB color development, the sections were differentiated with a differentiating solution and then turned blue. They were dehydrated and cleared. After the sections were air - dried, they were mounted, and the slides were read and interpreted under a microscope.\u003c/p\u003e\n\u003ch3\u003eInterpretation of immunohistochemical staining results\u003c/h3\u003e\n\u003cp\u003eThe positive products of p-STAT3 protein immunohistochemistry appear brownish-yellow or brownish-brown, mainly located in the nucleus. The results were interpreted blindly by two experienced pathologists using a semi-quantitative comprehensive scoring method: Four fields were randomly selected under a high-power microscope, and the grades were divided according to the positive staining intensity and positive area. Positive intensity: 0 points for basically no staining, 1 point for light yellow, 2 points for brownish-yellow, and 3 points for brownish-brown. Positive area: 0 points for \u0026le;\u0026thinsp;10%, 1 point for \u0026gt;\u0026thinsp;10% \u0026minus;\u0026thinsp;25%, 2 points for \u0026gt;\u0026thinsp;25% \u0026minus;\u0026thinsp;50%, and 3 points for \u0026gt;\u0026thinsp;50%. The total staining score is the product of the intensity score and the positive area score. A score of \u0026le;\u0026thinsp;3 is considered negative, and a score of \u0026ge;\u0026thinsp;4 is considered positive.\u003c/p\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n \u003cp\u003eAll data were entered using Excel and statistically analyzed using SPSS 27. Quantitative data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s), while categorical data were presented as the number of cases (percentage). Independent sample t - test was used for comparison between two groups of quantitative data, and Mann - Whitney U test was used for non - normal quantitative data. ANOVA was used for comparison among multiple groups, LSD - t test was used for pairwise comparison, and Kruskal - Wallis H test was used for non - normal quantitative data. Chi - square test was used for comparison of categorical data. Spearman correlation analysis was used to analyze the relationship between Helicobacter pylori infection and p - STAT3. Multivariate Logistic regression analysis was applied for multivariate analysis. A P - value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant for all statistical methods.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eBaseline Characteristics\u003c/h2\u003e\u003cp\u003eComparison of baseline data among the four groupsAccording to the inclusion and exclusion criteria, a total of 124 patients were enrolled, including: 31 cases in the cancer group, with 22 males and 9 females, aged 51\u0026ndash;79 (62.32\u0026thinsp;\u0026plusmn;\u0026thinsp;7.52) years; 31 cases in the high - grade group, with 23 males and 8 females, aged 52\u0026ndash;77 (62.0\u0026thinsp;\u0026plusmn;\u0026thinsp;7.43) years; 31 cases in the adenoma group, with 20 males and 11 females, aged 53\u0026ndash;78 (60.74\u0026thinsp;\u0026plusmn;\u0026thinsp;6.06) years; 31 cases in the control group, with 18 males and 13 females, aged 53\u0026ndash;71 (59.35\u0026thinsp;\u0026plusmn;\u0026thinsp;4.68) years. Comparison of the general data among the four groups showed that there were no statistically significant differences in gender, age, smoking history, drinking history, history of hypertension, history of diabetes and history of hyperuricemia among the four groups of patients (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). See Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of general data among the four groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003econtrol group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAdenoma group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh-level segment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCancer group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003ex\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e/F/H\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (male/female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18/13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20/11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23/8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22/9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.542\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e59.35\u0026thinsp;\u0026plusmn;\u0026thinsp;4.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.74\u0026thinsp;\u0026plusmn;\u0026thinsp;6.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e62.19\u0026thinsp;\u0026plusmn;\u0026thinsp;7.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e62.32\u0026thinsp;\u0026plusmn;\u0026thinsp;7.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.418\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.241\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esmoke(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5(16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(25.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(22.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5(16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.353\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.717\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ealcoholic consumption (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6(19.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6(19.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8(25.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.653\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.647\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehypertension(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(22.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11(35.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9(29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15(48.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e5.041\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.169\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ediabetes mellitus(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(9.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(22.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(22.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6(19.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.295\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.513\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehyperuricemia (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(9.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7(22.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3(9.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.931\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.402\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\u003eHp Infection and p-STAT3 Expression\u003c/h2\u003e\u003cp\u003eThe patients were classified by pathology to analyze the relationship between Helicobacter pylori infection, p-STAT3 positive and different colorectal lesions. The results showed that among H. pylori infections, the high-grade group (71.0%), cancer group (71.0%) vs control group (25.8%) statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); high-level group (71.0%), cancer group (71.0%) and adenoma group (29.0%), the difference was statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05); among p-STAT3 positive, the difference was statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) between high-grade group (64.5%), cancer group (74.2%) and control group (12.9%); the difference was statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) between high-grade group (64.5%), cancer group (74.2%) and adenoma group (29.0%); see Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\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 Helicobacter pylori infection and p-STAT3 positive in different colorectal diseases\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003econtrol group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAdenoma group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh-level segment\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCancer group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cem\u003ex\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHp positive(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(25.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22(71.0)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22(71)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e23.587\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ep-STAT3 positive(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(29.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20(64.5)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23(74.2)\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e31.521\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eNote: a indicates comparison with control group, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; b indicates comparison with adenoma group, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation analysis between Helicobacter pylori infection and p-STAT3\u003c/h2\u003e\u003cp\u003eSpearman correlation analysis was used to examine the relationship between Helicobacter pylori infection and p-STAT3. According to our data, there was a positive correlation between Hp positivity (%) and p-STAT3 positivity (%) (rs\u0026thinsp;=\u0026thinsp;0.209, P\u0026thinsp;=\u0026thinsp;0.02), as shown in 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 analysis between Helicobacter pylori infection and p-STAT3\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\"\u003e\u003cp\u003efactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHp positive(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-STAT3 positive(%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRs value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRs value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHp\u003c/p\u003e\u003cp\u003epositive(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.209\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ep-STAT3\u003c/p\u003e\u003cp\u003epositive(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.209\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.02\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\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=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation and Risk Factors\u003c/h2\u003e\u003cp\u003eIn the statistical analysis, factors with significant differences (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) such as HP infection and p - STAT3 were used as independent variables, and the occurrence of colorectal adenoma, high - grade lesions, and cancer were used as dependent variables for multivariate Logistic regression analysis to explore the independent risk factors for colorectal adenoma, colorectal high - grade lesions, and colorectal cancer. The results showed that HP infection and positive p - STAT3 were statistically significant independent risk factors for the colorectal cancer group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and HP infection and positive p - STAT3 were statistically significant independent risk factors for the colorectal high - grade lesion group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as shown in 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\u003eLogistic regression analysis of Hp and p - STAT3 in the adenoma group, high - grade group, and cancer group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003efactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003cp\u003evalue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSE\u003c/p\u003e\u003cp\u003evalue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWaldx\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003cp\u003evalue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003cp\u003evalue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003cp\u003evalue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95%CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdenoma group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHp\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.168\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.575\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.770\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e1.183\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.383\u0026ndash;3.650\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ep-STAT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.666\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.330\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e2.765\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.749\u0026ndash;10.203\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHigh-level segment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehp\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.968\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.619\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e10.093\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e7.155\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e2.125\u0026ndash;24.092\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ep-STAT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.523\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.688\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13.450\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e12.468\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e3.237\u0026ndash;48.018\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCancer group\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehp\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.971\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.638\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e9.539\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e7.179\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e2.055\u0026ndash;25.080\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ep-STAT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.981\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.708\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e17.736\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e19.715\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e4.923\u0026ndash;78.958\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":"Discussion","content":"\u003cp\u003eThe occurrence and development of colorectal cancer (CRC) is a complex, multi - stage and multi - factor - involved process, which encompasses multiple levels such as gene mutations, epigenetic alterations, and dysregulation of the microenvironment. The pathological evolution generally progresses from normal mucosa to abnormal hyperplasia and then to cancer. Colorectal adenoma with high - grade dysplasia is usually characterized by abnormal cell cycle regulation and significant atypia, but the basement membrane remains intact. We define this lesion as a precancerous lesion. Colorectal cancer originates from the epithelial cells of the colorectal mucosa and consists of cells and/or structures with malignant morphological features that penetrate the muscularis mucosa and infiltrate the submucosa or deeper layers.This study found that the Helicobacter pylori (Hp) infection rate was significantly higher in patients with colorectal adenoma with high - grade dysplasia or colorectal cancer than in those with colorectal adenoma or in normal individuals (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, the positive expression rate of p - STAT3 in the pathological specimens was significantly higher in patients with colorectal adenoma with high - grade dysplasia or colorectal cancer than in those with colorectal adenoma or in normal individuals (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Spearman's correlation analysis was used to examine the relationship between Hp infection and p - STAT3 expression, and a positive correlation was found between the percentage of Hp - positive cases and the percentage of p - STAT3 - positive cases (rs\u0026thinsp;=\u0026thinsp;0.209, P\u0026thinsp;=\u0026thinsp;0.02).Multivariate Logistic regression analysis showed that Helicobacter pylori (Hp) infection and positive p-STAT3 were independent risk factors for colorectal cancer and colorectal adenoma with high-grade dysplasia, which was statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The results of this study were highly consistent with recent large-scale population studies. Boustany et al. \u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003ebased on a cohort study of 47.71\u0026nbsp;million people, found that a history of Hp infection was significantly associated with the risk of colorectal cancer (OR\u0026thinsp;=\u0026thinsp;1.89), suggesting that Hp may promote carcinogenesis through direct or indirect mechanisms. A meta-analysis of the East Asian population showed that the association strength between Hp infection and colorectal cancer (OR\u0026thinsp;=\u0026thinsp;1.72) was higher than the global average \u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, which may be related to the virulence of region-specific strains or the host's genetic background. In addition, a systematic review by Liu et al. \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e indicated that Hp infection significantly increased the risk of colorectal adenoma (OR\u0026thinsp;=\u0026thinsp;1.67), especially high-grade dysplasia, supporting its role in the early stage of the \"adenoma-carcinoma\" sequence. Potential mechanisms of Hp infection activating the STAT3 pathway: (1) Chronic inflammation and cytokine release. Hp infection can induce chronic inflammation in the gastric mucosa and intestinal epithelium, promoting the secretion of pro-inflammatory factors (such as IL-6) \u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e. These cytokines activate JAK2 kinase by binding to cell membrane receptors, then phosphorylate STAT3 (p-STAT3) and promote its entry into the nucleus to regulate the transcription of target genes. In colorectal cancer, the IL-6/JAK2/STAT3 axis has been confirmed to promote cell proliferation and inhibit apoptosis \u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.(2) Direct effects of Hp virulence factors (such as cytotoxin-associated protein A). After being injected into host cells via the type IV secretion system, cytotoxin-associated gene A (CagA) can activate tyrosine family kinases \u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e, directly phosphorylate STAT3 independently of cytokine signals. Additionally, CagA can upregulate the expression of COX-2 \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e, promote the synthesis of prostaglandin E2 (PGE2), and further activate the STAT3 pathway.(3) Epigenetic regulation. Hp infection induces the silencing of miR490-3p. The downregulation of miR490-3p leads to an increase in the expression of DARPP-32. The elevated level of DARPP-32 protein triggers the continuous activation of the PI3K/AKT and STAT3 signaling pathways, specifically manifested as an increase in the levels of phosphorylated AKT (p-AKT) and phosphorylated STAT3 (p-STAT3) \u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.Pro-tumorigenic effects of the STAT3 pathway in colorectal cancer: (1) Anti-apoptosis: p-STAT3 upregulates anti-apoptotic proteins such as Bcl-2 and inhibits cell apoptosis \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. (2) Proliferation promotion: It activates genes such as Cyclin D1 and c-Myc to drive cell cycle progression \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e. (3) Immune escape: It induces the expression of PD-L1, inhibits T cell activity, and promotes immune suppression in the tumor microenvironment \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThis study found that Helicobacter pylori (Hp) infection and increased expression of p-STAT3 increased the risk of colorectal cancer (CRC) and colorectal adenoma with high-grade dysplasia, and were independent risk factors for both. There was a positive correlation between Hp infection and upregulated p-STAT3 expression in patients, suggesting that they may jointly participate in the occurrence and development of CRC and precancerous lesions. The occurrence and development of CRC are the result of the combined action of genes, environment, and microbiome. The average period from adenoma to carcinogenesis is about 10\u0026ndash;15 years. This finding provides new ideas for the early screening of high-risk populations for CRC. In addition, eradicating Hp infection or blocking the p-STAT3 pathway may become a new strategy for preventing or treating CRC, especially in areas with a high prevalence of Hp.\u003c/p\u003e\u003cp\u003eLimitations and recommendations: (1) The single-center design and small sample size may affect the universality of the results; (2) The upstream regulatory factors of STAT3 (such as IL-6 and JAK2) were not detected, which limited the depth of mechanism exploration. Future studies need to conduct multi-center, large-sample cohort validation. Moreover, exploring the predictive value of p-STAT3 expression combined with Hp infection status for the response to chemotherapy or immunotherapy will have important clinical significance.\u003c/p\u003e\u003cp\u003eIn conclusion,Helicobacter pylori (Hp) infection and increased expression of p-STAT3 increase the risk of colorectal cancer and colorectal adenoma with high-grade dysplasia and are independent risk factors for both. There is a positive correlation between Hp infection and upregulated p-STAT3 expression in patients, suggesting that the two may jointly participate in the occurrence and development of colorectal cancer and precancerous lesions.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCRC Colorectal cancer\u003c/p\u003e\n\u003cp\u003eHP Helicobacter pylori\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ep-STAT3 phosphorylated signal transducer and activator of transcription 3\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConceptualization:Zhongsen Dou \u0026nbsp;Fanglai Zhu.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFunding acquisition: Fanglai Zhu.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInvestigation: \u0026nbsp;Zhongsen Dou\u003c/p\u003e\n\u003cp\u003eMethodology:Zhongsen Dou,Lingrun Ye\u003c/p\u003e\n\u003cp\u003eResources: Fanglai Zhu,Zhongsen Dou\u003c/p\u003e\n\u003cp\u003eSupervision: Fanglai Zhu ,Lingrun Ye\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; original draft: \u0026nbsp; Zhongsen Dou\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; review \u0026amp; editing: Fanglai Zhu.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions\u003c/p\u003e\n\u003cp\u003eFLZ conceptualized the case report and did the procedure. ZSDand LRY prepared the initial drafting of the paper. ZSD and FLZ did the research, editing and final drafting of the paper. ZSD and FL Z contributed equally.All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis subject has been approved by the ethics committee of Anqing first people\u0026apos;s hospital. Written informed consent was obtained.\u003c/p\u003e\n\u003cp\u003eDeclaration of patient consent\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to concealtheir identity, but anonymity cannot be guaranteed.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eNil.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eAuthor details\u003c/p\u003e\n\u003cp\u003eThe first author \u0026nbsp;Zhongsen Dou：2023 graduate student of gastroenterology department\u0026nbsp;，Wannan Medical College，Wuhu，Anhui，China( e-mail: [email protected]）；\u003c/p\u003e\n\u003cp\u003eThe second author Lingrun Ye:2022 graduate student of gastroenterology department\u0026nbsp;，Wannan Medical College，Wuhu，Anhui，China(e-mail: [email protected]）；\u003c/p\u003e\n\u003cp\u003e* Correspondence: Fanglai Zhu, Department of Gastroenterology, Anqing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFirst People\u0026rsquo;s Hospital , Anqing 246000, China (e-mail: [email protected]).\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMorgan E, Arnold M, Gini A, Gut et al. 2023;72(2):338\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXu L, Zhao J, Li Z, et al. National and subnational incidence, mortality and associated factors of colorectal cancer in China: A systematic analysis and modelling study. J Glob Health. 2023;13:04096.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZygulska AL, Pierzchalski P. Novel Diagnostic Biomarkers in Colorectal Cancer. Int J Mol Sci. 2022;23(2):852.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMalfertheiner P, Camargo MC, El-Omar E, et al. Helicobacter pylori infection. Nat Rev Dis Primers. 2023;9(1):19.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSun Y, Gong W, Zhang S. METTL3 promotes colorectal cancer progression through activating JAK1/STAT3 signaling pathway. Cell Death Dis. 2023;14(11):765.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoustany A, Onwuzo S, Almomani A, Asaad I. Epidemiology and risk of colorectal cancer in patients with a history of Helicobacter pylori infection: a population-based study. Ann Gastroenterol. 2023;36(2):203\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMa L, Guo W, Zeng Z, Yang F, Tang S, Ling Y. Colorectal cancer risk in East Asian patients with Helicobacter pylori infection: A systematic review and meta-analysis. Med (Baltim). 2023;102(10):e33177.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu Y, Yang DQ, Jiang JN, Jiao Y. Relationship between Helicobacter pylori infection and colorectal polyp/colorectal cancer. World J Gastrointest Surg. 2024;16(4):1008\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGuo Y, Ding S. Helicobacter pylori Thioredoxin1 May Play a Highly Pathogenic Role via the IL6/STAT3 Pathway. Gastroenterol Res Pract. 2022;2022:3175935.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHuang B, Lang X, Li X. The role of IL-6/JAK2/STAT3 signaling pathway in cancers. Front Oncol. 2022;12:1023177.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang X, Soutto M, Chen Z et al. Induction of Fibroblast Growth Factor Receptor 4 by Helicobacter pylori via Signal Transducer and Activator of Transcription 3 With a Feedforward Activation Loop Involving SRC Signaling in Gastric Cancer [published correction appears in Gastroenterology. 2023;165(1):306. doi: 10.1053/j.gastro.2023.05.004.]. Gastroenterology. 2022;163(3):620\u0026ndash;636.e9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSakatani A, Hayashi Y, Saiki H, et al. A novel role for Helicobacter pylori cytotoxin-associated gene A in negative regulation of autophagy in human gastric cells. BMC Gastroenterol. 2023;23(1):326.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhu S, Khalafi S, Chen Z, et al. Silencing of miR490-3p by H. pylori activates DARPP-32 and induces resistance to gefitinib. Cancer Lett. 2020;491:87\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHsieh YC, Dai YC, Cheng KT, et al. Blockade of the SRC/STAT3/BCL-2 Signaling Axis Sustains the Cytotoxicity in Human Colorectal Cancer Cell Lines Induced by Dehydroxyhispolon Methyl Ether. Biomedicines. 2023;11(9):2530.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNing R, Chen G, Fang R, Zhang Y, Zhao W, Qian F. Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells. Biol Res. 2021;54(1):40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu C, Yao Z, Wang J, et al. Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway [published correction appears in. Cell Death Differ. 2020;27(7):2293.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Helicobacter pylori infection, p-STAT3, Colorectal cancer, Precancerous lesions, Correlation","lastPublishedDoi":"10.21203/rs.3.rs-6554594/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6554594/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThis study aimed to investigate the correlations among Helicobacter pylori (Hp) infection, p-STAT3, colon cancer and precancerous lesions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA total of 124 patients who underwent colonoscopy at the Endoscopy Center of Anqing First People's Hospital from January 2021 to June 2024 were enrolled. According to the pathological results of colonoscopy, the patients were divided into four groups: the adenoma group, the high-grade group, the cancer group and the control group. The expression of p-STAT3 and the status of Hp infection in each group were mainly observed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eIn Helicobacter pylori (Hp) infection, significant differences were observed between the high-grade group (71.0%), the cancer group (71.0%), and the control group (25.8%) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, there were significant differences between the high-grade group (71.0%), the cancer group (71.0%), and the adenoma group (29.0%) in Hp infection (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Regarding the positive expression of p-STAT3, significant differences were found between the high-grade group (64.5%), the cancer group (74.2%), and the control group (12.9%) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Moreover, significant differences existed between the high-grade group (64.5%), the cancer group (74.2%), and the adenoma group (29.0%) in the positive expression of p-STAT3 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Spearman correlation analysis was used to examine the relationship between Hp infection and p-STAT3, revealing a positive correlation between Hp positivity (%) and p-STAT3 positivity (%) (rs\u0026thinsp;=\u0026thinsp;0.209, P\u0026thinsp;=\u0026thinsp;0.02). Multivariate Logistic regression analysis indicated that Hp infection and p-STAT3 positivity were independent risk factors for the cancer group with statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and they were also independent risk factors for the high-grade group with statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eHelicobacter pylori (Hp) infection and increased expression of p-STAT3 increase the risk of colorectal cancer and colorectal adenoma with high-grade dysplasia and are independent risk factors for both. There is a positive correlation between Hp infection and upregulated p-STAT3 expression in patients, suggesting that the two may jointly participate in the occurrence and development of colorectal cancer and precancerous lesions.\u003c/p\u003e","manuscriptTitle":"Correlation analysis of Helicobacter pylori infection, p-STAT3 with colon cancer and precancerous lesions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 16:03:52","doi":"10.21203/rs.3.rs-6554594/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-08T08:20:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-20T08:57:19+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"63495502807435836100850074677932551654","date":"2026-03-13T13:31:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-10T02:47:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221227320292123976664655525377380946856","date":"2026-03-08T11:14:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-26T04:32:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-07T15:58:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-30T05:39:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-30T05:34:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cancer","date":"2025-04-29T09:01:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d499f22b-f119-4e2e-a3a7-bbafcde540b4","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-08T08:26:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-08 16:03:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6554594","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6554594","identity":"rs-6554594","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}