The Utility of Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Running Title: Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients

The Utility of Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Running Title: Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients | 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 Utility of Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Running Title: Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Nourhan Assem, Osama Ashraf Ahmed, Nada Mohamed Hassan Mohamed, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5706222/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 Background: Incidence of Hepatocellular carcinoma (HCC) has increased over the past few decades to become the most common primary hepatic malignancy. Most patients with HCC have advanced unresectable disease, resulting in limited treatment options with curative intent and poor survival outlooks . Results: In this study on Egyptian patients, hepatocellular carcinoma (HCC) primarily occurred in the sixth decade of life, often alongside liver cirrhosis. No significant gender or smoking differences were found between HCC and cirrhotic groups, suggesting smoking isn't a major HCC risk factor. Diabetes mellitus (DM) and hypertension (HTN) were more common in HCC patients, reflecting their roles in cirrhosis and HCC development. Serum alpha-fetoprotein (AFP) levels were significantly higher in HCC patients. Neuropilin-1, a novel marker, showed a significant increase in HCC patients compared to cirrhotic ones, with a strong correlation to liver function markers (AST, ALT, AFP, albumin) and Barcelona and Child scores. Neuropilin-1 demonstrated higher sensitivity (96.67%) and specificity (80%) for HCC detection compared to AFP, highlighting its potential as a superior biomarker for diagnosing HCC. Conclusion: Serum neuropilin 1 level was significantly higher in patients with HCC regardless presence of combined conditions as DM and HTN or viral markers and mildly elevated in patients with liver cirrhosis compared to HCC group. Neuropilin 1 is more sensitive and more specific than AFP. Using neuropilin 1 will improve the diagnostic field and can help in early detection of HCC in surveillance programs together with AFP. Serum Neuropilin 1 Diagnostic Marker Hepatocellular Carcinoma Egyptian Cirrhotic Figures Figure 1 Background HCC is the cause of >80% of primary liver cancer worldwide. HCC exacts a heavy disease burden and is a leading cause of cancer-related death in many parts of the world and is the fourth most common cause of cancer-related death overall worldwide (1). Alpha-fetoprotein (AFP) remains the most widely used serum biomarker for the diagnosis and prognosis of hepatocellular carcinoma (HCC). The role of AFP has become controversial due to nearly 30% of early-stage HCC patients being AFP negative (2). While NRP1 has been extensively studied and characterized, NRP2 has received fewer studies. Nonetheless, the significance of both NRPs in cancer, including HCC, has recently been highlighted due to their significant association with crucial cellular and molecular mechanisms involved in tumor progression ( 3 ). The role of Neuropilin 1 in the progression of HCC is not fully comprehended..NRP1 Expression has been detected in liver sinusoidal endothelial cells, in hepatic stellate cells, in the heap 129 hepatoma cell line, and was found to be increased following partial hepatectomy, under shear stress conditions and in liver cirrhosis although these data point out the important role of Neuropilin 1 in liver function and possible implication in liver carcinogenesis ( 4 ). METHODS Patients: This study had been carried out on 60, age range more than 18 year selected from internal medicine and hepatology outpatient clinics and inpatient wards at Ain shams university hospital from January 2024 to June 2024, after informed consent were taken from the patients Subjects were divided as follow: Group 1 : include 30 HCC diagnosed by alpha fetoprotein and imaging. Group 2 : include 30 matched cirrhotic patients without HCC divided according to child -Pugh scoring system. Methodology: Type of Study : Case control study Proposed Study Design: Comparative cross-sectional study Study Setting: After obtaining approval from the Research Ethical Committee of Ain Shams University, this study will be conducted in the Internal medicine and Hepatology department and outpatient clinic and clinical pathology lab at Ain Shams University Hospitals under supervision of Dr Mariem Elsaid lecturer clinical pathology at Ain Shams university. Study Period : 6 months Design: Study will be conducted on 60 Egyptian patients (30 HCC patients, 30 liver cirrhosis without HCC) Study Population: Cirrhotic Egyptian Patient Treated in Ain Shams University. Selection criteria for cases: Inclusion Criteria: Age > 18 years old and patients diagnosed with liver cirrhosis with or without HCC. Exclusion Criteria: age < 18 years old, pregnant, female, patients diagnosed with malignancy other than HCC and patients who refuse to participate in the study. Sample Size: 60 patients will be divided into 2 groups: Group A (Case): 30 patients with liver cirrhosis and Hepa-tocellular carcinoma. Group B (Control): 30 patients with liver cirrhosis with-out Hepatocellular carcinoma Ethical Considerations: A signed written consent will be taken from all participants included in the study. All data are confidential; patients will never be mentioned by name in any published paper. The Scientific Research Ethics Committee of the Faculty of Medicine of Ain Shams University will approve the study before commencing work. Amount of blood needed for research: 2 cm from each person. There will be no leftovers or storage of samples after doing research. Study Tools and procedures: All patients will be subjected to the following: Full medical history and full clinical examination including general and local examination. Laboratory assessment : CBC, PT, PTT, INR. Liver profile: AST, ALT, S. Albumin, T. Bilirubin, Bilirubin, ALP,Gamma GT. Kidney function tests: BUN, Creatinine. -Electro- Lytes: Na, K. HBsAg, HCV Ab. Alpha-feto protein (AFP) and Neuropilin 1. Radiological assessment: Pelviabdominal ultrasound, confirmation of any suspicious hepatic focal lesion by Triphasic CT with contrast or Dynamic MRI with contrast, statistical Analysis of all data to measure sensitivity and specificity of serum Neuropilin 1 diagnosing HCC and all personal protective equipment will be available and strict precautionary measures will be taken to ensure maximum safety for all participants and working staff. Principle of the assay: This kit is an Enzyme-Linked Immunosorbent Assay (ELISA). The plate has been pre-coated with Human NRP1 antibody. NRP1 present in the sample is added and binds to antibodies coated on the wells. And then biotinylated Human NRP1 Antibody is added and binds to NRP1 in the sample. Then Streptavidin-HRP is added and binds to the Biotinylated NRP1 antibody. After incubation unbound Streptavidin-HRP is washed away during a washing step. Substrate solution is then added, and color develops in proportion to the amount of Human NRP1. The reaction is terminated by addition of acidic stop solution and absorbance is measured at 450 nm. Statistical Methods: data was collected, revised, coded and entered to the Statistical Package for Social Science (IBM SPSS) version 27. The quantitative data were presented as mean, standard deviations and ranges when parametric and median, inter-quartile range (IQR) when data found non-parametric. Also, qualitative variables were presented as numbers and percentages. The comparison between groups regarding qualitative data was done by using Chi-square test and/or Fisher exact test when the expected count in any cell found less than 5. The comparison between two independent groups with quantitative data and parametric distribution was done by using independent t-test while with non-parametric distribution were done by using Mann-Whitney test. The comparison between more than two groups regarding quantitative data and non-parametric distribution was done by using Kruskall-Wallis test . Spearman correlation coefficients were used to assess the correlation between two quantitative parameters in the same group. Receiver operating characteristic curve (ROC) was used to assess the best cut off point with its sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) of the studied marker. The confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the p-value was considered significant as the following: P-value > 0.05: Non-significant (NS). P-value < 0.05: Significant (S). P-value < 0.01: Highly significant (HS). Results This study was carried out on 60 participants divided into 2 group: 30 patients cirrhotic with Hepatocellular Carcinoma. 30 cirrhotic patients without hepatocellular Carcinoma selected from Ain shams university hospitals, after informed consent were taken from the patients All patients were sex and age matched with average age of 61years old. HCC patients had significantly higher CHILD score with p value = 0.025 p value = 0.017., MELD score with p value = 0.017, AFP level with P value < 0,001, Neuropilin 1 level with P value < 0,001 Than cirrhotic patients. there was statistically significant positive correlation between: Neuropiln 1 and (AST, ALT, MELD) among all cases, neuropilin1 and (ALT) among cirrhotic group and neuropilin 1 and (ALT, AST, Barcelona score) among HCC group While there was statistically significant negative correlation between: Neuropiln 1 and (Albumin) among All cases There was no statistically significant correlation between: neuropiln 1 and (age, Hb, WBC, platelet, BUN, CR, total bilirubin, Direct bilirubin, NA, K, INR, child score) among ALL cases, neuropilin1 and (age, TLC, Hb, Platelet, BUN, CR, Direct bilirubin, AST,INR,CHILD, MELD,NA,K, total bilirubin) among cirrhotic group and neuropilin 1 and (age, TLC, Hb, Platelet, BUN, CR, Direct bilirubin, Total bilirubin, INR, CHILD,MELD,NA,K) among HCC group. The cut off point for neuropilin 1 level to differentiate between cases with HCC and cirrhotic cases was found > 10,7with sensitivity of 96,67%, specificity of 80% and area under curve (AUC) of 96,1%, AFP > 5,6 with sensitivity of 80%, specificity of 76,67% and AUC of 82,1%. DISCUSSION This study was carried out on 60 subjects, age range (28-91) year selected from Ain shams university hospitals, after informed written consent were taken from the patients, classified into 2 groups: Group A (HCC);30patients cirrhotic with hepatocellular carcinoma Group B (cirrhotic): 30 patients cirrhotic without hepatocellular carcinoma. In our study, we found that the serum AFP was significant increase in HCC patients compared to cirrhotic, this is in agreement with many several reports one of them is (5) that consider AFP in high serum levels as diagnostic for HCC combined with triphasic CT abdomen or dynamic MRI and many guidelines advised use of serum AFP combined with abdominal ultrasound for screening of cirrhotic patients for early detection of HCC as showed that AFP is still reliable marker in HCC. Regarding serum neuropilin1, which is the new marker addressed in this study, show that there was significant increase in neuropilin1 level in HCC group compared to cirrhotic with p value ˂ 0,001 agree with (6) that show in cross-sectional studies examining the association of neuropilin 1 with HCC, neuropilin 1 level was significantly higher in patients with HCC than in those cirrhotic. In our study we found that There was no statistically significant correlation between neuropilin 1 and (platelet, INR) among both HCC group and cirrhotic group against with (7 ) that found that negatively statistically significant correlation between neuropilin1 and platelet and positively statistically significant correlation between neuropilin1 and INR. In our study we found that there was no statistically Significant correlation between neuropilin 1 and (age, TLC, Hb, Creatinine) that agree with (6) and we found that no statistical correlation between neuropilin1 and bilirubin that agree with (8). In our study we found that there was a significant correlation between neuropilin 1 and (AST, ALT, AFP, albumin) that agree with (9) that found that there was significant correlation between neuropilin 1 and (AST, ALT, AFP, albumin). In our study there was positive significant correlation between MELD score and serum neuropilin level which agree with (7) and there was no significant correlation Between neuropilin1 level and CHILD score which agree with (6). In our study there was significant correlation between Barcelona score and neuropilin 1 which agree with (10) that was found Elevated serum neuropilin1 were detected in tumor stages B/C according to Barcelona staging system. Our study shows the sensitivity of serum neuropilin1 in detection of HCC was 96.67 % with specificity 80% with AUC 0.961 at cut off value > 10.7 ng / ml in compare with (6) That show serum neuropilin1 could detect HCC with sensitivity was 93.3% and specificity 80 % with AUC of 0.0842 at cut off value 4030 pg / ml. AFP in our study shows sensitivity in detection of HCC 80% with specificity 76,67% so AFP in our study show less sensitivity and specificity in detection of HCC than Neuropilin1 which agree with (9) that show serum NRP1 is a better diagnostic marker than AFP with an area under receiver operating curve of 0,971, compared with 0,862 for AFP. The limitations in the study include: 1 -small number of patients in our study. 2- No available investigation to exclude other malignancy like mammogram, colonoscopy. Conclusion Serum neuropilin 1 level was significantly higher in patients with HCC regardless presence of combined conditions as DM and HTN or viral markers and mildly elevated in patients with liver cirrhosis compared to HCC group. Neuropilin 1 is more sensitive and more specific than AFP. Using neuropilin 1 will improve the diagnostic field and can help in early detection of HCC in surveillance programs together with AFP. Abbreviations AFP: Alpha-feto protein AST: Aspartate aminotransferase ALT: Alanine transaminase AUC: Area under curve BCLC: Barcelona Clinic Liver Cancer CBC: complete blood picture Cr: creatinine Db: Direct bilirubin HB: hemoglobin HCC: Hepatocellular carcinoma INR: International normalized ratio K: potassium NRP: Neuropilin NA: sodium Tb: total bilirubin Tlc: total leucocytic count Declarations Ethics approval and consent to participate: This study had been performed in accordance with the ethical standards. Faculty of Medicine, Ain Shams University Ethical Committee approval was taken before starting the study, and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. A written consent was obtained from each participant. Committee’s reference number :FWA000017585 Consent for publication: not applicable Availability of data and material: data are available with corresponding author to be presented upon request. Competing interests: the authors declare that they have no competing interests Funding: no funding was obtained for this study Author contribution: N A drafted the manuscript and supervised the study, OA designed the study, N m did data analysis and interpretation and KA did critical revision of the manuscript for important intellectual content. All authors read the article and accepted it Acknowledgements: thanks, should be applied to clinical pathology staff at Ain Shams University for their help in facilitating data collection. References Yang JD, Hainaut P, Gores GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenteroly Hepatol 2019; 16, 589–604. Thokerunga, E., Kisembo, P., FangFang, H. et al . Serum Midkine for AFP-negative hepatocellular carcinoma diagnosis: a systematic review and meta-analysis. Egypt Liver Journal 13, 25 (2023) Fernández-Palanca P, Payo-Serafín T, Méndez-Blanco C, San-Miguel B, Tuñón MJ, González-Gallego J, Mauriz JL. Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications. Clinical and Molecular Hepatology. 2023; 29(2):293. Bergé M, Allanic D, Bonnin P, de Montrion C, Richard J, Suc M, Boivin JF, Contrerès JO, Lockhart BP, Pocard M, Lévy BI, Tucker GC, Tobelem G, Merkulova-Rainon T et al. Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling. J Hepatol. 2011; 55(4):866-75. Jasirwan COM, Fahira A, Siregar L, Loho I et al. The alpha-fetoprotein serum is still reliable as a biomarker for the surveillance of hepatocellular carcinoma in Indonesia. BMC Gastroenterol. 2020 Jul 9;20(1):215. doi: 10.1186/s12876-020-01365-1. PMID: 32646378; PMCID: PMC7346661. Mostafa SE, Hany RE, Yasser MI, Ahmed EM, et al. Neuropilin1 as a Diagnostic Marker for Hepatocellular Carcinoma. BMFJ 2022; 39(2): 515-528. Hoda AM and Dalia AM. The significance of neuropilin-1 for the diagnosis of hepatocellular carcinoma in egyptian patients. GSJ , 2019; 7 (10): 2320-2336. Lin J, Zhang Y, Wu J, Li L, Chen N, Ni P, Song L, Liu X et al. Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma. Clin Chim Acta. 2018; 485:158-165. Jiafei L, Yingwei Z, Jiemin W, Li L, Ning C, Peihua N, Lihua S, Xiangfan L, et al. Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma,Clinica Chimica Acta, 2018; 485: 158-165. Abdel Ghafar MT, Elkhouly RA, Elnaggar MH et al . Utility of Serum Neuropilin-1 and Angiopoietin-2 as Markers of Hepatocellular Carcinoma. Journal of Investigative Medicine . 2021;69(6):1222-1229. Tables Table 1: Comparison between Group A (HCC) and Group B (Cirrhotic) regarding (Cbc, Liver profile, Kidney function, electrolyte, INR, AFP, Neuropilin 1) Median (IQR) Median (IQR) value p value sig. Cirrhotic HCC Mann Whitney test tlc 4.5 (3.7 - 8.2) 5 (3.9 - 6.4) z = -0.17 0.865 NS Hb 10.85 (9 – 12) 11.15 (9.6 - 13) z = -1.243 0.214 NS plt 119.5 (64 - 177) 134.5 (90 - 181) z = -0.92 0.355 NS BUN 21.5 (14 - 34) 25 (19 - 30) z = -0.8 0.424 NS CR 0.9 (0.7 - 1.3) 0.9 (0.7 – 1.1) z = -0.601 0.548 NS NA 135.5 (132 - 137) 132.5 (130 - 135) z = -1.51 0.130 NS K 4.1 (3.5 – 4.6) 4 (3.3 – 4.3) z = -1.044 0.296 NS Tb 2.2 (0.8 - 5.7) 1 (0.7 - 2.1) z = -1.47 0.141 NS Db 0.85 (0.3 - 2.4) 0.5 (0.3 - 0.7) z = -1.34 0.180 NS AST 39 (29 - 85) 47 (27 - 70) z = -0.08 0.935 NS ALT 26.5 (12 - 53) 35.5 (17 - 51) z = -1.21 0.228 NS Albumin 2.85 (2.3 – 3.7) 3.15 (2.46 – 3.6) z = -0.844 0.398 NS INR 1.5 (1.20 – 1.6) 1.2 (1.2 – 1.53) z = -1.492 0.136 NS AFP 2.65 (1.65 – 5.6) 39.5 (5.8 - 350) z = -4.266 <0.001 S Neuropilin1 (ng/ml) 5.65 (4.23 - 10.65) 42.19 (23.97 - 49) z = -6.14 <0.001 S Table2: Correlation of Neuropilin 1 level with other studied parameters among all cases, group A (HCC) and group B (cirrhotic) Neuropilin1 (ng/ml) Whole sample (N=60) Cirrhotic (N=30) HCC (N=30) r P-value Sig. r P-value Sig. r P-value Sig. Age 0.132 0.313 NS 0.240 0.201 NS -0.158 0.405 NS TLC 0.049 0.712 NS 0.073 0.700 NS 0.016 0.934 NS Hb 0.243 0.062 NS 0.332 0.073 NS 0.079 0.680 NS Platelets 0.104 0.431 NS 0.097 0.611 NS -0.017 0.931 NS BUN 0.210 0.107 NS 0.089 0.640 NS 0.324 0.081 NS CR -0.079 0.546 NS -0.048 0.801 NS -0.028 0.883 NS NA -0.194 0.138 NS 0.088 0.642 NS -0.192 0.308 NS K -0.122 0.351 NS -0.233 0.215 NS 0.149 0.433 NS Total bilirubin -0.137 0.296 NS -0.197 0.297 NS 0.270 0.149 NS Direct bilirubin -0.178 0.174 NS -0.196 0.299 NS 0.091 0.631 NS AST 0.310* 0.016 S 0.315 0.090 NS 0.671** 0.000 HS ALT 0.504** 0.000 HS 0.601** 0.000 HS 0.704** 0.000 HS Albumin -0.274* 0.034 S -0.689** 0.000 HS -0.561** 0.001 HS INR -0.131 0.318 NS 0.102 0.593 NS 0.050 0.794 NS CHILD score 0.123 0.350 NS -0.245 0.192 NS 0.057 0.764 NS MELD score 0.482* 0.000 HS 0.149 0.433 NS 0.186 0.324 NS Table3: Correlation of Neuropilin 1 level with BARCELONA score in group A (HCC) Neuropilin1 (ng/ml) Kruskal-Wallis test Median (IQR) k P-value Sig. BARCELONA A 16.94 (13.48 – 19.63) 20.855 <0.001 HS B 31.38 (26.63 – 36.12) C 48 (42.09 – 49) D 50 (50 – 51) 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-5706222","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":406726905,"identity":"df7e3299-7379-44ff-8c96-1b33be5906c9","order_by":0,"name":"Nourhan Assem","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIiWNgGAWjYJACZijNeIChAsRlbiBaC8MBhjMgLiMpWhjbwLbh12LO3mP2uaDmDgN/A/ODw7zzaqP524FaflRsw6nFsueM8ewZx54xSBxgMzjMu+147ozDjA2MPWdu49RicCPHmJmH7TDIIyAtx3IbgFqYGdsIafl3mEH+APuHw7xzjuXOJ0oLb9thBoMDPEBbGmpyNxDUcuZYMTNv32Eew8M8BQfnHDuQuxGo5SBevxxv3szM8+2wnNzx9o0P3tTU5c47f/jggx8VuLXAAA8odph4GA6DeQcIqocBxh8MdUQrHgWjYBSMgpEDAMHEWvAFbnaZAAAAAElFTkSuQmCC","orcid":"","institution":"Ain Shams University","correspondingAuthor":true,"prefix":"","firstName":"Nourhan","middleName":"","lastName":"Assem","suffix":""},{"id":406726906,"identity":"e1d90a26-64c7-4581-a3fc-7de9f33b4f7c","order_by":1,"name":"Osama Ashraf Ahmed","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Osama","middleName":"Ashraf","lastName":"Ahmed","suffix":""},{"id":406726907,"identity":"34bf96dd-0f03-4a1e-8306-f8fbb6cfee8c","order_by":2,"name":"Nada Mohamed Hassan Mohamed","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Nada","middleName":"Mohamed Hassan","lastName":"Mohamed","suffix":""},{"id":406726908,"identity":"b51c4856-ab6a-48fd-ac23-2dca7f3071a9","order_by":3,"name":"Kareem Ahmed Mahmoud","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Kareem","middleName":"Ahmed","lastName":"Mahmoud","suffix":""}],"badges":[],"createdAt":"2024-12-24 12:38:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5706222/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5706222/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74912833,"identity":"42057ab6-7d17-4431-be28-2fe9938545e1","added_by":"auto","created_at":"2025-01-28 09:24:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":36468,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig.2: \u003c/strong\u003eROC curve to assess neuropilin 1 and AFP levels to differentiate between Group A (HCC) and Group B (Cirrhotic)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5706222/v1/cfd09ea473daeeb81329d29f.png"},{"id":74914804,"identity":"bbf44edc-5b35-40c6-a148-d9625575dca1","added_by":"auto","created_at":"2025-01-28 09:40:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1068108,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5706222/v1/d594d9d7-412e-4315-b3be-ec3c6e810192.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Utility of Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Running Title: Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients","fulltext":[{"header":"Background","content":"\u003cp\u003eHCC is the cause of \u0026gt;80% of primary liver cancer worldwide. HCC exacts a heavy disease burden and is a leading cause of cancer-related death in many parts of the world and is the fourth most common cause of cancer-related death overall worldwide \u003cstrong\u003e\u003cem\u003e(1).\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlpha-fetoprotein (AFP) remains the most widely used serum biomarker for the diagnosis and prognosis of hepatocellular carcinoma (HCC). The role of AFP has become controversial due to nearly 30% of early-stage HCC patients being AFP negative \u003cstrong\u003e\u003cem\u003e(2).\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWhile NRP1 has been extensively studied and characterized, NRP2 has received fewer studies. Nonetheless, the significance of both NRPs in cancer, including HCC, has recently been highlighted due to their significant association with crucial cellular and molecular mechanisms involved in tumor progression \u003cstrong\u003e\u003cem\u003e(\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e).\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe role of Neuropilin 1 in the progression of HCC is not fully comprehended..NRP1 Expression has been detected in liver sinusoidal endothelial cells, in hepatic stellate cells, in the heap 129 hepatoma cell line, and was found to be increased following partial hepatectomy, under shear stress conditions and in liver cirrhosis although these data point out the important role of Neuropilin 1 in liver function and possible implication in liver carcinogenesis \u003cstrong\u003e\u003cem\u003e(\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e4\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e).\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003ePatients:\u003c/u\u003e\u003c/strong\u003eThis study had been carried out on 60, age range more than 18 year selected from internal medicine and hepatology outpatient clinics and inpatient wards at Ain shams university hospital from January 2024 to June 2024, after informed consent were taken from the patients\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubjects were divided as follow: Group 1\u003c/strong\u003e: include 30 HCC diagnosed by alpha fetoprotein and imaging. \u003cstrong\u003eGroup 2\u003c/strong\u003e: include 30 matched cirrhotic patients without HCC divided according to child -Pugh scoring system.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eMethodology:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eType of Study\u003c/u\u003e\u003c/strong\u003e\u003cu\u003e:\u003c/u\u003e Case control study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eProposed Study Design:\u003c/u\u003e\u003c/strong\u003e Comparative cross-sectional study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStudy Setting:\u003c/u\u003e\u003c/strong\u003eAfter obtaining approval from the Research Ethical Committee of Ain Shams University, this study will be conducted in the Internal medicine and Hepatology department and outpatient clinic and clinical pathology lab at Ain Shams University Hospitals under supervision of Dr Mariem Elsaid lecturer clinical pathology at Ain Shams university.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStudy Period\u003c/u\u003e\u003c/strong\u003e: 6 months\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eDesign:\u003c/u\u003e\u003c/strong\u003eStudy will be conducted on 60 Egyptian patients (30 HCC patients, 30 liver cirrhosis without HCC)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStudy Population:\u003c/u\u003e\u003c/strong\u003e Cirrhotic Egyptian Patient Treated in Ain Shams University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eSelection criteria for cases:\u003c/u\u003e\u003c/strong\u003e \u003cstrong\u003e\u003cem\u003e\u003cu\u003eInclusion Criteria:\u003c/u\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eAge \u0026gt; 18 years old and patients diagnosed with liver cirrhosis with or without HCC. \u003cstrong\u003e\u003cu\u003eExclusion Criteria:\u003c/u\u003e\u003c/strong\u003e age \u0026lt; 18 years old, pregnant, female, patients diagnosed with malignancy other than HCC and patients who refuse to participate in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eSample Size:\u003c/u\u003e\u003c/strong\u003e60 patients will be divided into 2 groups: \u003cstrong\u003eGroup A (Case):\u0026nbsp;\u003c/strong\u003e30 patients with liver cirrhosis and Hepa-tocellular carcinoma. \u003cstrong\u003eGroup B (Control):\u0026nbsp;\u003c/strong\u003e30 patients with liver cirrhosis with-out Hepatocellular carcinoma\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eEthical Considerations:\u003c/u\u003e\u003c/strong\u003eA signed written consent will be taken from all participants included in the study.\u003c/p\u003e\n\u003cp\u003eAll data are confidential; patients will never be mentioned by name in any published paper.\u003c/p\u003e\n\u003cp\u003eThe Scientific Research Ethics Committee of the Faculty of Medicine of Ain Shams University will approve the study before commencing work.\u003c/p\u003e\n\u003cp\u003eAmount of blood needed for research: 2 cm from each person.\u003c/p\u003e\n\u003cp\u003eThere will be no leftovers or storage of samples after doing research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStudy Tools and procedures:\u003c/u\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eAll patients will be subjected to the following:\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eFull medical history and full clinical examination including general and local examination. \u003cstrong\u003eLaboratory assessment\u003c/strong\u003e: CBC, PT, PTT, INR. Liver profile: AST, ALT, S. Albumin, T. Bilirubin, Bilirubin, ALP,Gamma GT. Kidney function tests: BUN, Creatinine. -Electro- Lytes: Na, K. HBsAg, HCV Ab. Alpha-feto protein (AFP) and Neuropilin 1. \u003cstrong\u003eRadiological assessment:\u0026nbsp;\u003c/strong\u003ePelviabdominal ultrasound, confirmation of any suspicious hepatic focal lesion by Triphasic CT with contrast or Dynamic MRI with contrast, statistical Analysis of all data to measure sensitivity and specificity of serum Neuropilin 1 diagnosing HCC and all personal protective equipment will be available and strict precautionary measures will be taken to ensure maximum safety for all participants and working staff.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003ePrinciple of the assay:\u003c/u\u003e\u003c/strong\u003e This kit is an Enzyme-Linked Immunosorbent Assay (ELISA). The plate has been pre-coated with Human NRP1 antibody. NRP1 present in the sample is added and binds to antibodies coated on the wells. And then biotinylated Human NRP1 Antibody is added and binds to NRP1 in the sample. Then Streptavidin-HRP is added and binds to the Biotinylated NRP1 antibody. After incubation unbound Streptavidin-HRP is washed away during a washing step. Substrate solution is then added, and color develops in proportion to the amount of Human NRP1. The reaction is terminated by addition of acidic stop solution and absorbance is measured at 450 nm.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eStatistical Methods:\u003c/u\u003e\u003c/strong\u003edata was collected, revised, coded and entered to the Statistical Package for Social Science (IBM SPSS) version 27. The quantitative data were presented as mean, standard deviations and ranges when parametric and median, inter-quartile range (IQR) when data found non-parametric. Also, qualitative variables were presented as numbers and percentages.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe comparison between groups regarding qualitative data was done by using \u003cstrong\u003e\u003cem\u003eChi-square test\u003c/em\u003e\u003c/strong\u003eand/or \u003cstrong\u003e\u003cem\u003eFisher exact test\u003c/em\u003e\u003c/strong\u003e when the expected count in any cell found less than 5.\u003c/p\u003e\n\u003cp\u003eThe comparison between two independent groups with quantitative data and parametric distribution was done by using \u003cstrong\u003e\u003cem\u003eindependent t-test\u0026nbsp;\u003c/em\u003e\u003c/strong\u003ewhile with non-parametric distribution were done by using \u003cstrong\u003e\u003cem\u003eMann-Whitney test.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe comparison between more than two groups regarding quantitative data and non-parametric distribution was done by using \u003cstrong\u003e\u003cem\u003eKruskall-Wallis test\u003c/em\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSpearman correlation coefficients\u003c/em\u003e\u003c/strong\u003e were used to assess the correlation between two quantitative parameters in the same group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eReceiver operating characteristic curve (ROC)\u003c/em\u003e\u003c/strong\u003e was used to assess the best cut off point with its sensitivity, specificity, positive predictive value, negative predictive value and area under curve (AUC) of the studied marker.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe confidence interval was set to 95% and the margin of error accepted was set to 5%. So, the p-value was considered significant as the following: P-value \u0026gt; 0.05: Non-significant (NS). P-value \u0026lt; 0.05: Significant (S). P-value \u0026lt; 0.01: Highly significant (HS).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThis study was carried out on 60 participants divided into 2 group: 30 patients cirrhotic with Hepatocellular Carcinoma. 30 cirrhotic patients without hepatocellular Carcinoma selected from Ain shams university hospitals, after informed consent were taken from the patients All patients were sex and age matched with average age of 61years old.\u003c/p\u003e \u003cp\u003eHCC patients had significantly higher CHILD score with p value\u0026thinsp;=\u0026thinsp;0.025 p value\u0026thinsp;=\u0026thinsp;0.017., MELD score with p value\u0026thinsp;=\u0026thinsp;0.017, AFP level with P value\u0026thinsp;\u0026lt;\u0026thinsp;0,001, Neuropilin 1 level with P value\u0026thinsp;\u0026lt;\u0026thinsp;0,001\u003c/p\u003e \u003cp\u003eThan cirrhotic patients.\u003c/p\u003e \u003cp\u003ethere was statistically significant positive correlation between: Neuropiln 1 and (AST, ALT, MELD) among all cases, neuropilin1 and (ALT) among cirrhotic group and neuropilin 1 and (ALT, AST, Barcelona score) among HCC group\u003c/p\u003e \u003cp\u003eWhile there was statistically significant negative correlation between: Neuropiln 1 and (Albumin) among All cases\u003c/p\u003e \u003cp\u003eThere was no statistically significant correlation between: neuropiln 1 and (age, Hb, WBC, platelet, BUN, CR, total bilirubin, Direct bilirubin, NA, K, INR, child score) among ALL cases, neuropilin1 and (age, TLC, Hb, Platelet, BUN, CR, Direct bilirubin, AST,INR,CHILD, MELD,NA,K, total bilirubin) among cirrhotic group and neuropilin 1 and (age, TLC, Hb, Platelet, BUN, CR, Direct bilirubin, Total bilirubin, INR, CHILD,MELD,NA,K) among HCC group.\u003c/p\u003e \u003cp\u003eThe cut off point for neuropilin 1 level to differentiate between cases with HCC and cirrhotic cases was found\u0026thinsp;\u0026gt;\u0026thinsp;10,7with sensitivity of 96,67%, specificity of 80% and area under curve (AUC) of 96,1%, AFP\u0026thinsp;\u0026gt;\u0026thinsp;5,6 with sensitivity of 80%, specificity of 76,67% and AUC of 82,1%.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study was carried out on 60 subjects, age range (28-91) year selected from Ain shams university hospitals, after informed written consent were taken from the patients, classified into 2 groups:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGroup A (HCC);30patients cirrhotic with hepatocellular carcinoma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGroup B (cirrhotic): 30 patients cirrhotic without hepatocellular carcinoma.\u003c/p\u003e\n\u003cp\u003eIn our study, we found that the serum AFP was significant increase in HCC patients compared to cirrhotic, this is in agreement with many several reports one of them is \u003cstrong\u003e\u003cem\u003e(5)\u003c/em\u003e\u003c/strong\u003e that consider AFP in high serum levels as diagnostic for HCC combined with triphasic CT abdomen or dynamic MRI and many guidelines advised use of serum AFP combined with abdominal ultrasound for screening of cirrhotic patients for early detection of HCC as showed that AFP is still reliable marker in HCC.\u003c/p\u003e\n\u003cp\u003eRegarding serum neuropilin1, which is the new marker addressed in this study, show that there was significant increase in neuropilin1 level in HCC group compared to cirrhotic with p value ˂ 0,001 agree with \u003cstrong\u003e\u003cem\u003e(6)\u003c/em\u003e\u003c/strong\u003e that show in cross-sectional studies examining the association of neuropilin 1 with HCC, neuropilin 1 level was significantly higher in patients with HCC than in those cirrhotic.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study we found that There was no statistically significant correlation between neuropilin 1 and (platelet, INR) among both HCC group and cirrhotic group against with \u003cstrong\u003e\u003cem\u003e(7\u003c/em\u003e\u003c/strong\u003e) that found that negatively statistically significant correlation between neuropilin1 and platelet and positively statistically significant correlation between neuropilin1 and INR.\u003c/p\u003e\n\u003cp\u003eIn our study we found that there was no statistically Significant correlation between neuropilin 1 and (age, TLC, Hb, Creatinine) that agree with \u003cstrong\u003e\u003cem\u003e(6)\u003c/em\u003e\u003c/strong\u003e and we found that no statistical correlation between neuropilin1 and bilirubin that agree with \u003cstrong\u003e\u003cem\u003e(8).\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn our study we found that there was a significant correlation between neuropilin 1 and (AST, ALT, AFP, albumin) that agree with \u003cstrong\u003e\u003cem\u003e(9)\u003c/em\u003e\u003c/strong\u003e that found that there was significant correlation between neuropilin 1 and (AST, ALT, AFP, albumin).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study there was positive significant correlation between MELD score and serum neuropilin level which agree with\u003cstrong\u003e\u003cem\u003e\u0026nbsp;(7)\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eand there was no significant correlation Between neuropilin1 level and CHILD score which agree with \u003cstrong\u003e\u003cem\u003e(6).\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn our study there was significant correlation between Barcelona score and neuropilin 1 which agree with \u003cstrong\u003e\u003cem\u003e(10)\u003c/em\u003e\u003c/strong\u003e that was found Elevated serum neuropilin1 were detected in tumor stages B/C according to Barcelona staging system.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study shows the sensitivity of serum neuropilin1 in detection of HCC was 96.67 % with specificity 80% with AUC 0.961 at cut off value \u0026gt; 10.7 ng / ml in compare with \u003cstrong\u003e\u003cem\u003e(6)\u003c/em\u003e\u003c/strong\u003e That show serum neuropilin1 could detect HCC with sensitivity was 93.3% and specificity 80 % with AUC of 0.0842 at cut off value 4030 pg / ml.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAFP in our study shows sensitivity in detection of HCC 80% with specificity 76,67% so AFP in our study show less sensitivity and specificity in detection of HCC than Neuropilin1 which agree with \u003cstrong\u003e\u003cem\u003e(9)\u003c/em\u003e\u003c/strong\u003e that show serum NRP1 is a better diagnostic marker than AFP with an area under receiver operating curve of 0,971, compared with 0,862 for AFP.\u003c/p\u003e\n\u003cp\u003eThe limitations in the study include:\u003c/p\u003e\n\u003cp\u003e1 -small number of patients in our study.\u003c/p\u003e\n\u003cp\u003e2- No available investigation to exclude other malignancy like mammogram, colonoscopy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSerum neuropilin 1 level was significantly higher in patients with HCC regardless presence of combined conditions as DM and HTN or viral markers and mildly elevated in patients with liver cirrhosis compared to HCC group. Neuropilin 1 is more sensitive and more specific than AFP. Using neuropilin 1 will improve the diagnostic field and can help in early detection of HCC in surveillance programs together with AFP.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAFP: Alpha-feto protein\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAST: Aspartate aminotransferase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;ALT: Alanine transaminase\u003c/p\u003e\n\u003cp\u003eAUC: Area under curve\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBCLC:\u0026nbsp;\u0026nbsp;Barcelona Clinic Liver Cancer\u003c/p\u003e\n\u003cp\u003eCBC: complete blood picture\u003c/p\u003e\n\u003cp\u003eCr: creatinine\u003c/p\u003e\n\u003cp\u003eDb: Direct bilirubin\u003c/p\u003e\n\u003cp\u003eHB: hemoglobin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHCC: Hepatocellular carcinoma\u003c/p\u003e\n\u003cp\u003eINR: International normalized ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eK: potassium\u003c/p\u003e\n\u003cp\u003eNRP: Neuropilin\u003c/p\u003e\n\u003cp\u003eNA: sodium\u003c/p\u003e\n\u003cp\u003eTb: total bilirubin\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Tlc: total leucocytic count\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u0026nbsp;Ethics\u0026nbsp;approval and consent to participate: This study had been performed in accordance with the ethical standards. Faculty of Medicine, Ain Shams University Ethical Committee approval was taken before starting the study, and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. A written consent was obtained from each participant.\u003c/p\u003e\n\u003cp\u003eCommittee’s reference number :FWA000017585\u003c/p\u003e\n\u003cp\u003eConsent for publication: not applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and material: data are available with corresponding author to be presented upon request.\u003c/p\u003e\n\u003cp\u003eCompeting interests: the authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003eFunding: no funding was obtained for this study\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eAuthor contribution: N A \u0026nbsp; drafted the manuscript and supervised the study, OA designed the study, N m did data analysis and interpretation and KA did critical revision of the manuscript for important intellectual content. All authors read the article and accepted it\u003c/li\u003e\n \u003cli\u003eAcknowledgements: thanks, should be applied to clinical pathology staff at Ain Shams University for their help in facilitating data collection. \u0026nbsp;\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eYang JD, Hainaut P, Gores GJ, \u003cem\u003eet al.\u003c/em\u003e A global view of hepatocellular carcinoma: trends, risk, prevention and management. \u003cem\u003eNat Rev Gastroenteroly Hepatol\u003c/em\u003e 2019; 16, 589\u0026ndash;604.\u003c/li\u003e\n \u003cli\u003eThokerunga, E., Kisembo, P., FangFang, H. \u003cem\u003eet al\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e Serum Midkine for AFP-negative hepatocellular carcinoma diagnosis: a systematic review and meta-analysis. \u003cem\u003eEgypt Liver Journal\u003c/em\u003e 13, 25 (2023)\u003c/li\u003e\n \u003cli\u003eFern\u0026aacute;ndez-Palanca P, Payo-Seraf\u0026iacute;n T, M\u0026eacute;ndez-Blanco C, San-Miguel B, Tu\u0026ntilde;\u0026oacute;n MJ, Gonz\u0026aacute;lez-Gallego J, Mauriz JL. Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications. Clinical and Molecular Hepatology. 2023; 29(2):293.\u003c/li\u003e\n \u003cli\u003eBerg\u0026eacute; M, Allanic D, Bonnin P, de Montrion C, Richard J, Suc M, Boivin JF, Contrer\u0026egrave;s JO, Lockhart BP, Pocard M, L\u0026eacute;vy BI, Tucker GC, Tobelem G, Merkulova-Rainon T et al. Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling. J Hepatol. 2011; 55(4):866-75.\u003c/li\u003e\n \u003cli\u003eJasirwan COM, Fahira A, Siregar L, Loho I et al. The alpha-fetoprotein serum is still reliable as a biomarker for the surveillance of hepatocellular carcinoma in Indonesia. BMC Gastroenterol. 2020 Jul 9;20(1):215. doi: 10.1186/s12876-020-01365-1. PMID: 32646378; PMCID: PMC7346661.\u003c/li\u003e\n \u003cli\u003eMostafa SE, Hany RE, Yasser MI, Ahmed EM, et al. Neuropilin1 as a Diagnostic Marker for Hepatocellular Carcinoma. BMFJ 2022; 39(2): 515-528.\u003c/li\u003e\n \u003cli\u003eHoda AM and Dalia AM. The significance of neuropilin-1 for the diagnosis of hepatocellular carcinoma in egyptian patients. \u003cem\u003eGSJ\u003c/em\u003e, 2019; \u003cem\u003e7\u003c/em\u003e(10): 2320-2336.\u003c/li\u003e\n \u003cli\u003eLin J, Zhang Y, Wu J, Li L, Chen N, Ni P, Song L, Liu X et al. Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma. Clin Chim Acta. 2018; 485:158-165.\u003c/li\u003e\n \u003cli\u003eJiafei L, Yingwei Z, Jiemin W, Li L, Ning C, Peihua N, Lihua S, Xiangfan L, et al. Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma,Clinica Chimica Acta, 2018; 485: 158-165.\u003c/li\u003e\n \u003cli\u003eAbdel Ghafar MT, Elkhouly RA, Elnaggar MH\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003eet al . Utility of Serum Neuropilin-1 and Angiopoietin-2 as Markers of Hepatocellular Carcinoma. \u003cem\u003eJournal of Investigative Medicine\u003c/em\u003e. 2021;69(6):1222-1229.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1:\u0026nbsp;\u003c/strong\u003eComparison between Group A (HCC) and Group B (Cirrhotic) regarding (Cbc, Liver profile, Kidney function, electrolyte, INR, AFP, Neuropilin 1)\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"114%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 23px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003esig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCirrhotic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHCC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMann Whitney test\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003etlc\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e4.5 (3.7 - 8.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e5 (3.9 - 6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.865\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e10.85 (9 \u0026ndash; 12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e11.15 (9.6 - 13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -1.243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eplt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e119.5 (64 - 177)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e134.5 (90 - 181)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eBUN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e21.5 (14 - 34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e25 (19 - 30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.9 (0.7 - 1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.9 (0.7 \u0026ndash; 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -0.601\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e135.5 (132 - 137)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e132.5 (130 - 135)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e4.1 (3.5 \u0026ndash; 4.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e4 (3.3 \u0026ndash; 4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -1.044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eTb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e2.2 (0.8 - 5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1 (0.7 - 2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -1.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eDb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.85 (0.3 - 2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e0.5 (0.3 - 0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e39 (29 - 85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e47 (27 - 70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e26.5 (12 - 53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e35.5 (17 - 51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -1.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eAlbumin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e2.85 (2.3 \u0026ndash; 3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e3.15 (2.46 \u0026ndash; 3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -0.844\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.398\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eINR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.5 (1.20 \u0026ndash; 1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e1.2 (1.2 \u0026ndash; 1.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003ez = -1.492\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAFP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.65 (1.65 \u0026ndash; 5.6)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e39.5 (5.8 - 350)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ez = -4.266\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeuropilin1 (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5.65 (4.23 - 10.65)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e42.19 (23.97 - 49)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ez = -6.14\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eTable2:\u0026nbsp;\u003c/strong\u003eCorrelation of Neuropilin 1 level with other studied parameters among all cases, group A (HCC) and group B (cirrhotic)\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"109%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 18px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"9\" style=\"width: 81px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeuropilin1 (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 27px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWhole sample (N=60)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCirrhotic (N=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHCC (N=30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.405\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eTLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.712\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.934\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.680\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003ePlatelets\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.931\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eBUN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.640\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e-0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.546\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.801\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.883\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e-0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.642\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e-0.122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.351\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.215\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eTotal bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e-0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eDirect bilirubin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e-0.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 6px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e-0.196\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.299\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.631\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003eAST\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n 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6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 5px;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eTable3:\u0026nbsp;\u003c/strong\u003eCorrelation of Neuropilin 1 level with BARCELONA score in group A (HCC)\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"521\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNeuropilin1 (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\"\u003e\n \u003cp\u003e\u003cstrong\u003eKruskal-Wallis test\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ek\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eP-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSig.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003eBARCELONA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16.94 (13.48 \u0026ndash; 19.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e20.855\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eHS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e31.38 (26.63 \u0026ndash; 36.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48 (42.09 \u0026ndash; 49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e50 (50 \u0026ndash; 51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Serum Neuropilin 1, Diagnostic Marker, Hepatocellular Carcinoma, Egyptian Cirrhotic","lastPublishedDoi":"10.21203/rs.3.rs-5706222/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5706222/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eIncidence of Hepatocellular carcinoma (HCC) has increased over the past few decades to become the most common primary hepatic malignancy. Most patients with HCC have advanced unresectable disease, resulting in limited treatment options with curative intent and poor survival outlooks\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In this study on Egyptian patients, hepatocellular carcinoma (HCC) primarily occurred in the sixth decade of life, often alongside liver cirrhosis. No significant gender or smoking differences were found between HCC and cirrhotic groups, suggesting smoking isn't a major HCC risk factor. Diabetes mellitus (DM) and hypertension (HTN) were more common in HCC patients, reflecting their roles in cirrhosis and HCC development. Serum alpha-fetoprotein (AFP) levels were significantly higher in HCC patients. Neuropilin-1, a novel marker, showed a significant increase in HCC patients compared to cirrhotic ones, with a strong correlation to liver function markers (AST, ALT, AFP, albumin) and Barcelona and Child scores. Neuropilin-1 demonstrated higher sensitivity (96.67%) and specificity (80%) for HCC detection compared to AFP, highlighting its potential as a superior biomarker for diagnosing HCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eSerum neuropilin 1 level was significantly higher in patients with HCC regardless presence of combined conditions as DM and HTN or viral markers and mildly elevated in patients with liver cirrhosis compared to HCC group. Neuropilin 1 is more sensitive and more specific than AFP. Using neuropilin 1 will improve the diagnostic field and can help in early detection of HCC in surveillance programs together with AFP.\u003c/p\u003e","manuscriptTitle":"The Utility of Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Running Title: Serum Neuropilin 1 as a Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-28 09:24:33","doi":"10.21203/rs.3.rs-5706222/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":"84e54d56-ea16-4052-a507-1b0b590dec98","owner":[],"postedDate":"January 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-28T09:24:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-28 09:24:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5706222","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5706222","identity":"rs-5706222","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}