The Utility of Serum Neuropilin 1 as a Diagnostic Biomarker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients

The Utility of Serum Neuropilin 1 as a Diagnostic Biomarker 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 Biomarker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients Nourhan Assem Ali, Osama A. Ahmed, Nada M. H. Mohamed, Kareem A. M. Abdelnabi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6959946/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/Aims: In recent decades, hepatocellular carcinoma has become the prevailing type of primary hepatic cancer, with its incidence rising dramatically. Many HCC patients are identified at an advanced, inoperable stage, limiting curative treatment options and resulting in poor survival rates. Methods: This case control study encompassed 60 individuals, aged 18 and above, recruited from the hepatology and internal medicine clinics and hospital units between January 2024 and June 2024 at Ain Shams University Hospital. The patients were classified as follows: Group 1 consisted of 30 HCC patients through alpha-fetoprotein testing and imaging. Group 2 comprised 30 cirrhotic patients, devoid of HCC, matched and categorized following the Child-Pugh scoring system Results: This investigation of Egyptian patients found that HCC typically emerges in the sixth decade of life and is often linked to liver cirrhosis. Patients with HCC exhibited significantly elevated serum alpha-fetoprotein (AFP) levels. Moreover, Neuropilin-1 (NRP1), a recently discovered biomarker, showed a substantial increase in HCC patients compared to cirrhosis patients. This elevation correlated strongly with liver function indicators (AST, ALT, AFP, albumin) and Barcelona and Child-Pugh scores. NRP1 demonstrated superior sensitivity (96.67%) and specificity (80%) in diagnosing HCC, unlike AFP, highlighting its capability as a more effective indicator for diagnosing HCC. Conclusion: Serum NRP1 levels were notably elevated in HCC patients. In contrast, cirrhotic patients showed only a slight increase in NRP1 levels compared to the HCC group. Hepatocellular Carcinoma Egyptian Cirrhotic Serum Neuropilin 1 Diagnostic Biomarker Figures Figure 1 Introduction Hepatocellular carcinoma represents close to 80% of the global incidence of primary hepatic cancer. It is a considerable health challenge and is a primary contributor to cancer-related mortality in numerous areas. Globally, HCC is the fourth prevailing reason for cancer-linked deaths 1 . Alpha-fetoprotein (AFP) is the prevailing blood-based marker utilized for HCC diagnosis and prognosis. Nevertheless, the reliability of AFP has been questioned, as approximately 30% of patients with early-stage HCC do not exhibit detectable AFP levels 2 . While NRP1 has been extensively studied and documented, NRP2 has received less attention. Nevertheless, recent studies have underscored the importance of both neuropilins (NRPs) in cancer, including HCC, due to their robust connection with essential tumor development-derived cytological and molecular functions 3 . The function of NRP1 in the HCC progression remains inadequately elucidated. NRP1 expression has been found in the cellular environment of liver sinusoids, including endothelial and stellate cells and the Hepa 129 hepatoma cell line. Its levels have been manifested to rise under shear stress conditions, after partial hepatectomy, and liver cirrhosis, indicating its contribution in NRP1 in hepatic function and its potential association with liver carcinogenesis 4 . Subjects and Methods This case-control studywas previously posted as a preprint version on research square (DOI: 10.21203/rs.3.rs-5706222/v1), on 28 th of December 2024. Participants: This study encompassed 60 individuals, aged 18 and above, recruited from the hepatology and internal medicine clinics and hospital units between January 2024 and June 2024 at Ain Shams University Hospital. All subjects provided informed consent. The 60 Egyptian patients were classified as follows: Group 1 consisted of 30 HCC patients through alpha-fetoprotein testing and imaging. Group 2 comprised 30 cirrhotic patients, devoid of HCC, matched and categorized following the Child-Pugh scoring system. Setting of the Study: This study was performed in the Hepatology and Internal Medicine Department, outpatient clinic, and clinical pathology lab at Ain Shams University Hospitals, under the supervision of Dr. Mariem Elsaid, Lecturer of Clinical Pathology at Ain Shams University. Inclusion and Exclusion Criteria: The study encompassed liver cirrhosis patients over 18 years old, with or without HCC were included. While the encompassed individuals under 18 years old, pregnant women, malignant patients other than HCC, and those who decline participation were excluded. Sample Distribution : The 60 patients will be allocated into two groups: Group A (Case) comprised of 30 patients experienced both liver cirrhosis and HCC, whereas Group B (Control) consisted of 30 liver cirrhosis patients without HCC. Ethical Protocol : All study participants provided written informed consent. Confidentiality was maintained, with no patient names disclosed in any publications. The study commenced only after approval from the Scientific Research Ethics Committee of Ain Shams University's Faculty of Medicine (Ethical number FWA000017585- Ethical approval date 17-1-2024). Each participant contributed 2 cm of blood for research purposes, with no sample storage or remnants after the study. Study Tools and procedures: Participants underwent comprehensive medical history taking and thorough clinical examinations. Laboratory tests encompassed coagulation studies (PT, PTT, INR), complete blood count, kidney function tests (BUN, creatinine), electrolytes (Na, K), liver function tests (ALT, direct bilirubin, AST, serum albumin, and total bilirubin), and tumor markers (Alpha-fetoprotein and NRP1). Imaging studies involved pelviabdominal ultrasound and any identified liver abnormalities warranting further investigation were assessed using contrast-enhanced triphasic computed tomography or dynamic magnetic resonance imaging. Data analysis assessed the sensitivity and specificity of serum NRP1 in diagnosing HCC. Stringent safety measured and personal protective equipment was employed to ensure participant and staff safety. Assay Principle: Enzyme-Linked Immunosorbent Assay (ELISA) was utilized to quantify Human NRP1(Bioassay Technology Laboratory (BT Lab), Shanghai, China). The process involved binding sample NRP1 to pre-coated antibodies, followed by addition of biotinylated Human NRP1 Antibody, which bind to Streptavidin-HRP upon adding it. A substrate solution was added after washing, producing color proportional to NRP1 concentration. Afterward, an acidic stop solution was introduced, halting the reaction, and the absorbance was quantified at 450 nm. Statistical Methods : The gathered information was examined, encoded, and input into IBM SPSS version 27. For parametric distributions, quantitative data were summarized using means, standard deviations, and ranges, while medians and interquartile ranges (IQR) were utilized for non-parametric distributions. Qualitative variables were reported using percentages and frequencies. The Chi-square test was employed to compare qualitative data between groups, whereas Fisher's exact test was utilized when expected cell counts fell below 5. To compare two independent groups, the independent t-test and Mann-Whitney test were employed for parametric quantitative and non-parametric data, respectively. The Kruskal-Walli’s test was employed for comparisons among many groups with non-parametric quantitative data. Spearman's correlation coefficients were employed to evaluate the correlations between two quantitative variables within a single group. The receiver operating characteristic curve was deployed to ascertain the optimal threshold, in addition to evaluating negative and positive predictive values, specificity, sensitivity, and the area under the curve for marker under examination. A 95% confidence interval and 5% error margin were applied. Significance levels were defined as: P > 0.05 (non-significant, NS), P < 0.05 (significant, S), and P< 0.01 (highly significant, HS) Results Here, we enrolled 60 subjects, evenly allocated into: 30 cirrhotic patients experiencing HCC and 30 cirrhotic patients without HCC. Participants were enrolled from Ain Shams University Hospitals following the acquisition of informed consent. All patients were matched according to sex and age (a mean age: 61 years). Furthermore, HCC patients exhibited a significant rise in AFP and NRP1 level, unlike cirrhotic patients, devoid of HCC. Moreover, NRP1 demonstrated significant positive connections with (AST, ALT, MELD) among all cases, NRP1 and ALT in the cirrhotic group, and NRP1 and (ALT, AST, Barcelona score) in the HCC group. Conversely, among all cases, NRP1 revealed a statistically significant adverse connection with Albumin (Table 1 ). Table 1 Comparison between Group A (HCC) and Group B (Cirrhotic) regarding (Liver profile, Complete blood picture, 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 platelet 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 0.13 NS K 4.1 (3.5–4.6) 4 (3.3–4.3) z = -1.044 0.296 NS Total bilirubin 2.2 (0.8–5.7) 1 (0.7–2.1) z = -1.47 0.141 NS Direct bilirubin 0.85 (0.3–2.4) 0.5 (0.3–0.7) z = -1.34 0.18 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 TLC: Total leucocytic count, Hb: Hemoglobin, BUN: Blood urea nitrogen CR: Creatine, Na: Sodium, K: potassium, AST: Aspartate aminotransferase, ALT: Alanine transaminase, INR: International normalized ratio, and AFP: Alpha-feto protein No statistically significant correlations were found between NRP1 and (Hb, TLC, platelet, BUN, CR, TB, DB, NA, K, INR, child score) among all cases. Similarly, no significant correlations were observed between NRP1 and (TLC, Hb, Platelet, BUN, CR, DB, AST, INR, CHILD, MELD, NA, K, TB) in the cirrhotic group, or between NRP1 and (TLC, Hb, Platelet, BUN, CR, DB, TB, INR, CHILD, MELD, NA, K) in the HCC group (Table 2 ). Table 2 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. TLC 0.049 0.712 NS 0.073 0.7 NS 0.016 0.934 NS Hb 0.243 0.062 NS 0.332 0.073 NS 0.079 0.68 NS Platelets 0.104 0.431 NS 0.097 0.611 NS -0.017 0.931 NS BUN 0.21 0.107 NS 0.089 0.64 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 0.27 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 0.09 NS 0.671** 0 HS ALT 0.504** 0 HS 0.601** 0 HS 0.704** 0 HS Albumin -0.274* 0.034 S -0.689** 0 HS -0.561** 0.001 HS INR -0.131 0.318 NS 0.102 0.593 NS 0.05 0.794 NS CHILD score 0.123 0.35 NS -0.245 0.192 NS 0.057 0.764 NS MELD score 0.482* 0 HS 0.149 0.433 NS 0.186 0.324 NS TLC: Total leucocytic count, Hb: Hemoglobin, BUN: Blood urea nitrogen CR: Creatine, Na: Sodium, K: potassium, AST: Aspartate aminotransferase, ALT: Alanine transaminase, INR: International normalized ratio, and AFP: Alpha-feto protein Significant Correlation between Neuropilin 1 level with BARCELONA score in group A (HCC) (p < 0.001) (Table 3 ). Table 3 Correlation of Neuropilin 1 level with BARCELONA score in group A (HCC) Neuropilin1 (ng/ml) Kruskal-Walli’s test Median (IQR) k P-value Sig. BARCELONA A 16.94 (13.48–19.63) 20.855 10,7, with 96,67% sensitivity, 80% specificity, and AUC of 96,1%. For AFP, the threshold was > 5,6, with 80% sensitivity, 76,67% specificity, and an AUC of 82,1% (Fig. 1 and Table 4 ). Table 4 Comparative Diagnostic Accuracy of AFP and Neuropilin-1 for Detecting Hepatocellular Carcinoma Cut off point AUC 95% CI Sensitivity Specificity +PV -PV P-value AFP > 5.6 0.821 0.700 to 0.908 80 76.67 77.4 79.3 10.7 0.961 0.877 to 0.994 96.67 80 82.9 96 < 0.001 Discussion This study included 60 subjects aged 28 to 91 years, recruited from Ain Shams University hospitals following the acquisition of written informed consent. The participants were categorized into (30 subjects/group): Group A (HCC): Cirrhotic patients with HCC and Group B (cirrhotic): cirrhotic patients, devoid of HCC. Our research revealed a notable elevation in serum AFP levels among HCC patients, unlike cirrhotic patients. This observation aligned with several studies, including one 5 that recognizes elevated serum AFP as a diagnostic indicator for HCC when used in conjunction with triphasic CT abdomen or dynamic MRI. Furthermore, various guidelines suggest combining serum AFP with abdominal ultrasound for screening cirrhotic patients to enable early HCC detection. These outcomes reinforce the ongoing AFP reliability as an HCC indicator. Regarding serum NRP1, a novel marker examined in this study, our results showed that the HCC group demonstrated significantly elevated NRP1 levels contrasted with the cirrhotic group ( P -value < 0.001), corroborating a previous study 6 , which demonstrated through cross-sectional analyses that HCC patients experienced significantly greater NRP1 levels than cirrhosis patients. Our research revealed no statistically significant connection between NRP1, and platelet count or INR in both HCC and cirrhotic groups. This finding contradicts a previous study 7 , which reported a significant inverse correlation with platelet count and a positive correlation with INR. We found no statistically significant relationship between NRP1 and factors such as total leucocytic count (TLC), hemoglobin (Hb), and creatinine, aligned with earlier study 6 . Furthermore, our study manifested no statistical correlation between NRP1 and bilirubin, aligning with the findings in 8 . Our research identified that NRP1 experienced a significant correlation with AST, ALT, AFP, and albumin, which agrees with the findings of 8 . We observed that MELD score had a positive and significant association with serum NRP1 levels, supporting the results of 7 . However, no significant connection between NRP1 levels and CHILD score was observed, which is consistent with the findings reported in 6 . Our outcomes revealed that the Barcelona score had a significant correlation with NRP1 levels, aligning with the results of 9 , which noted elevated serum NRP1 levels in tumor stages B/C per the Barcelona staging system. In our research, serum NRP1 manifested high sensitivity (96.67%) and specificity (80%) in detecting HCC, with an AUC of 0.961 at a threshold value > 10.7 ng/ml. This compares to the findings of 6 , which reported a sensitivity 93.3% and specificity 80% (AUC = 0.842, threshold value = 4030 pg/ml). Herein, we manifested that AFP exhibited a sensitivity (80%) and specificity (76.67%) in detecting HCC, indicating lower performance compared to NRP1. This supports the findings of 8 , which suggested that serum NRP1 serves as a superior diagnostic indicator compared to AFP, with an AUC of 0.971 for NRP1 versus 0.862 for AFP. Limitations of our study encompass of a small patient sample size and lack of investigations to exclude other malignancies, such as mammograms or colonoscopies. Conclusion Serum NRP1 levels were markedly greater in HCC patients and slightly elevated in liver cirrhotic patients but remained lower than those in the HCC group. NRP1 exhibited superior sensitivity and specificity compared to AFP. Integrating NRP1 into diagnostic protocols could improve HCC detection and facilitate early identification in surveillance programs, especially when used in conjunction with AFP. Abbreviations AFP Alpha-feto protein AST Aspartate aminotransferase ALT Alanine transaminase AUC Area under curve 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 was conducted per Declaration of Helsinki (1975) and the Ethical Committee of the Faculty of Medicine at Ain Shams University, that approved the study prior to the study commencement. Each participant provided written consent. Ethical number : FWA000017585 ( Ethical approval date : 17/1/2024 ) Publication Consent: Not Applicable. Funding: No Fund References Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 16, 589–604 (2019). Thokerunga E, Kisembo P, Fang Fang H, Wang Z, Zhang Y, Bongolo CC, et al. Serum Midkine for AFP-negative hepatocellular carcinoma diagnosis: a systematic review and meta-analysis. Egypt Liver J 2023; 13:25. Fernández-Palanca P, Payo-Serafín T, Méndez-Blanco C, San-Miguel B, Tuñón MJ, González-Gallego J, et al. Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications. Clin Mol Hepatol 2023; 29:293. Bergé M, Allanic D, Bonnin P, de Montrion C, Richard J, Suc M, et al. Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling. J Hepatol . 2011; 55(4):866-875. Jasirwan COM, Fahira A, Siregar L, Loho I. The alpha-fetoprotein serum is still reliable as a biomarker for the surveillance of hepatocellular carcinoma in Indonesia . BMC Gastroenterol. 2020;20(1):215. Mostafa SE, Hany RE, Yasser MI, Ahmed EM. Neuropilin1 as a Diagnostic Marker for Hepatocellular Carcinoma . Benha medical journal . 2022;39(2):515-28. Hoda AM and Dalia AM. The significance of neuropilin-1 for the diagnosis of hepatocellular carcinoma in Egyptian patients. Global scientific journal, 2019; 7 (10): 2320-2336. Lin J, Zhang Y, Wu J, Li L, Chen N, Ni P, et al. Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma. Clin Chim Acta . 2018; 485:158-65. Abdel Ghafar MT, Elkhouly RA, Elnaggar MH, Mabrouk MM, Darwish SA, Younis RL, et al. Utility of serum neuropilin-1 and angiopoietin-2 as markers of hepatocellular carcinoma. J Investig Med . 2021;69(6):1222-29. 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-6959946","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":481896451,"identity":"c4e7ec8a-8fcd-4dce-af4c-c98f90a1b893","order_by":0,"name":"Nourhan Assem Ali","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":"Assem","lastName":"Ali","suffix":""},{"id":481896452,"identity":"4ab1d335-d670-48f4-ac0c-87b3f3bf7182","order_by":1,"name":"Osama A. Ahmed","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Osama","middleName":"A.","lastName":"Ahmed","suffix":""},{"id":481896453,"identity":"f989c3b1-df88-4505-87a7-a1351515e9ac","order_by":2,"name":"Nada M. H. Mohamed","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Nada","middleName":"M. H.","lastName":"Mohamed","suffix":""},{"id":481896454,"identity":"ad43bb11-18f6-4b78-a958-6eb0b4ce7cf9","order_by":3,"name":"Kareem A. M. Abdelnabi","email":"","orcid":"","institution":"Ain Shams University","correspondingAuthor":false,"prefix":"","firstName":"Kareem","middleName":"A. M.","lastName":"Abdelnabi","suffix":""}],"badges":[],"createdAt":"2025-06-23 21:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6959946/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6959946/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86643932,"identity":"b71f8da4-0671-4672-b6bc-b3f3cf27621a","added_by":"auto","created_at":"2025-07-14 08:38:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":25553,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve to assess neuropilin 1 and AFP levels to differentiate between Group A (HCC) and Group B (Cirrhotic)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6959946/v1/34172e5618f9963b657845cc.png"},{"id":89912362,"identity":"5842a0e0-7d45-4895-85ce-7b0b022ba63e","added_by":"auto","created_at":"2025-08-26 11:08:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":831807,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6959946/v1/bc8b81fd-da42-4bb0-a781-77e6096bac79.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThe Utility of Serum Neuropilin 1 as a Diagnostic Biomarker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHepatocellular carcinoma represents close to 80% of the global incidence of primary hepatic cancer. It is a considerable health challenge and is a primary contributor to cancer-related mortality in numerous areas. Globally, HCC is the fourth prevailing reason for cancer-linked deaths \u003cstrong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/strong\u003e. Alpha-fetoprotein (AFP) is the prevailing blood-based marker utilized for HCC diagnosis and prognosis. Nevertheless, the reliability of AFP has been questioned, as approximately 30% of patients with early-stage HCC do not exhibit detectable AFP levels \u003cstrong\u003e\u003csup\u003e2\u003c/sup\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eWhile NRP1 has been extensively studied and documented, NRP2 has received less attention. Nevertheless, recent studies have underscored the importance of both neuropilins (NRPs) in cancer, including HCC, due to their robust connection with essential tumor development-derived cytological and molecular functions\u003cstrong\u003e\u0026nbsp;\u003csup\u003e3\u003c/sup\u003e\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eThe function of NRP1 in the HCC progression remains inadequately elucidated. NRP1 expression has been found in the cellular environment of liver sinusoids, including endothelial and stellate cells and the Hepa 129 hepatoma cell line. Its levels have been manifested to rise under shear stress conditions, after partial hepatectomy, and liver cirrhosis, indicating its contribution in NRP1 in hepatic function and its potential association with liver carcinogenesis \u003cstrong\u003e\u003csup\u003e4\u003c/sup\u003e\u003c/strong\u003e.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cp\u003eThis case-control studywas previously posted as a preprint version on research square (DOI: 10.21203/rs.3.rs-5706222/v1), on 28\u003csup\u003eth\u003c/sup\u003e of December 2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants:\u003c/strong\u003e This study encompassed 60 individuals, aged 18 and above, recruited from the hepatology and internal medicine clinics and hospital units between January 2024 and June 2024\u0026nbsp;\u003cbr\u003eat Ain Shams University Hospital. All subjects provided informed consent. The 60 Egyptian patients were classified as follows: \u003cstrong\u003eGroup 1\u003c/strong\u003e consisted of 30 HCC patients through alpha-fetoprotein testing and imaging. \u003cstrong\u003eGroup 2\u003c/strong\u003e comprised 30 cirrhotic patients, devoid of HCC, matched and categorized following the Child-Pugh scoring system.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSetting of the Study:\u0026nbsp;\u003c/strong\u003eThis study was performed in the Hepatology and Internal Medicine Department, outpatient clinic, and clinical pathology lab\u0026nbsp;at Ain Shams University Hospitals, under the supervision of Dr. Mariem Elsaid, Lecturer of Clinical Pathology at Ain Shams University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInclusion and Exclusion Criteria:\u003c/strong\u003e The study encompassed liver cirrhosis patients over 18 years old, with or without HCC were included. While the encompassed individuals under 18 years old, pregnant women, malignant patients other than HCC, and those who decline participation were excluded.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample Distribution\u003c/strong\u003e: The 60 patients will be allocated into two groups: Group A (Case) comprised of 30 patients experienced both liver cirrhosis and HCC, whereas Group B (Control) consisted of 30 liver cirrhosis patients\u0026nbsp;without HCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Protocol\u003c/strong\u003e: All study participants provided written informed consent. Confidentiality was maintained, with no patient names disclosed in any publications. The study commenced only after approval from the Scientific Research Ethics Committee of Ain Shams University's Faculty of Medicine (Ethical number FWA000017585- Ethical approval date 17-1-2024). Each participant contributed 2 cm of blood for research purposes, with no sample storage or remnants after the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Tools and procedures:\u003c/strong\u003e Participants underwent comprehensive medical history taking and thorough clinical examinations. Laboratory tests encompassed coagulation studies (PT, PTT, INR), complete blood count, kidney function tests (BUN, creatinine), electrolytes (Na, K), liver function tests (ALT, direct bilirubin, AST, serum albumin, and total bilirubin), and tumor markers (Alpha-fetoprotein and NRP1). Imaging studies involved pelviabdominal ultrasound and any identified liver abnormalities warranting further investigation were assessed using contrast-enhanced triphasic computed tomography or dynamic magnetic resonance imaging. Data analysis assessed the sensitivity and specificity of serum NRP1 in diagnosing HCC. Stringent safety measured and personal protective equipment was employed to ensure participant and staff safety.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssay Principle:\u003c/strong\u003e Enzyme-Linked Immunosorbent Assay (ELISA) was utilized to quantify Human NRP1(Bioassay Technology Laboratory (BT Lab), Shanghai, China). The process involved binding sample NRP1 to pre-coated antibodies, followed by addition of biotinylated Human NRP1 Antibody, which bind to Streptavidin-HRP upon adding it. A substrate solution was added after washing, producing color proportional to NRP1 concentration. Afterward, an acidic stop solution was introduced, halting the reaction, and the absorbance was quantified at 450 nm.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Methods\u003c/strong\u003e: The gathered information was examined, encoded, and input into IBM SPSS version 27. For parametric distributions, quantitative data were summarized using means, standard deviations, and ranges, while medians and interquartile ranges (IQR) were utilized for non-parametric distributions. Qualitative variables were reported using percentages and\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;frequencies. The Chi-square test was employed to compare qualitative data between groups, whereas Fisher's exact test was utilized when expected cell counts fell below 5. To compare two independent groups, the independent t-test and Mann-Whitney test were employed for parametric quantitative and non-parametric data, respectively. The Kruskal-Walli’s test was employed for comparisons among many groups with non-parametric quantitative data. Spearman's correlation coefficients were employed to evaluate the correlations between two quantitative variables within a single group. The receiver operating characteristic curve was deployed to ascertain the optimal threshold, in addition to evaluating negative and positive predictive values, specificity, sensitivity, and the area under the curve for marker under examination. A 95% confidence interval and 5% error margin were applied. Significance levels were defined as: P \u0026gt; 0.05 (non-significant, NS), P \u0026lt; 0.05 (significant, S), and P\u0026lt; 0.01 (highly significant, HS)\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eHere, we enrolled 60 subjects, evenly allocated into: 30 cirrhotic patients experiencing HCC and 30 cirrhotic patients without HCC. Participants were enrolled from Ain Shams University Hospitals following the acquisition of informed consent. All patients were matched according to sex and age (a mean age: 61 years). Furthermore, HCC patients exhibited a significant rise in AFP and NRP1 level, unlike cirrhotic patients, devoid of HCC. Moreover, NRP1 demonstrated significant positive connections with (AST, ALT, MELD) among all cases, NRP1 and ALT in the cirrhotic group, and NRP1 and (ALT, AST, Barcelona score) in the HCC group. Conversely, among all cases, NRP1 revealed a statistically significant adverse connection with Albumin (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\u003e\u003cb\u003eComparison between Group A (HCC) and Group B (Cirrhotic) regarding (Liver profile, Complete blood picture, Kidney function, electrolyte, INR, AFP, Neuropilin 1\u003c/b\u003e)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMedian (IQR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMedian (IQR)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003evalue\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003esig.\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCirrhotic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHCC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u003cp\u003eMann Whitney test\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTLC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.5 (3.7\u0026ndash;8.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3.9\u0026ndash;6.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.865\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.85 (9\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.15 (9.6\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -1.243\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.214\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eplatelet\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e119.5 (64\u0026ndash;177)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e134.5 (90\u0026ndash;181)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.355\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBUN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.5 (14\u0026ndash;34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (19\u0026ndash;30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.424\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.9 (0.7\u0026ndash;1.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.9 (0.7\u0026ndash;1.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -0.601\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.548\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e135.5 (132\u0026ndash;137)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e132.5 (130\u0026ndash;135)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -1.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.1 (3.5\u0026ndash;4.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3.3\u0026ndash;4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -1.044\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.296\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.2 (0.8\u0026ndash;5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.7\u0026ndash;2.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.141\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDirect bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.85 (0.3\u0026ndash;2.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5 (0.3\u0026ndash;0.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -1.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (29\u0026ndash;85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47 (27\u0026ndash;70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.935\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.5 (12\u0026ndash;53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.5 (17\u0026ndash;51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -1.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.228\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.85 (2.3\u0026ndash;3.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.15 (2.46\u0026ndash;3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -0.844\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.398\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.5 (1.20\u0026ndash;1.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.2 (1.2\u0026ndash;1.53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -1.492\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAFP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.65 (1.65\u0026ndash;5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.5 (5.8\u0026ndash;350)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -4.266\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuropilin1 (ng/ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5.65 (4.23\u0026ndash;10.65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42.19 (23.97\u0026ndash;49)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ez = -6.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eTLC: Total leucocytic count, Hb: Hemoglobin, BUN: Blood urea nitrogen CR: Creatine, Na: Sodium, K: potassium, AST: Aspartate aminotransferase, ALT: Alanine transaminase, INR: International normalized ratio, and AFP: Alpha-feto protein\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNo statistically significant correlations were found between NRP1 and (Hb, TLC, platelet, BUN, CR, TB, DB, NA, K, INR, child score) among all cases. Similarly, no significant correlations were observed between NRP1 and (TLC, Hb, Platelet, BUN, CR, DB, AST, INR, CHILD, MELD, NA, K, TB) in the cirrhotic group, or between NRP1 and (TLC, Hb, Platelet, BUN, CR, DB, TB, INR, CHILD, MELD, NA, K) in the HCC group (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\u003eCorrelation of Neuropilin 1 level with other studied parameters among all cases, group A (HCC) and group B (cirrhotic).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\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=\"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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"9\" nameend=\"c10\" namest=\"c2\"\u003e\u003cp\u003eNeuropilin1 (ng/ml)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eWhole sample (N\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eCirrhotic (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u003cp\u003eHCC (N\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSig.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSig.\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eSig.\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTLC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.049\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.712\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.073\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.934\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.243\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.332\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.073\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.079\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelets\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.104\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.431\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.097\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.611\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-0.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.931\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBUN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.107\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.089\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.324\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.081\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.079\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.546\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.048\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.801\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-0.028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.883\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.194\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.642\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-0.192\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.308\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.122\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.351\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.233\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.215\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.149\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.433\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.296\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.197\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.297\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.149\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDirect bilirubin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.178\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.174\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.196\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.299\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.091\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.631\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.310*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.315\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.671**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eALT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.504**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.601**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.704**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.274*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.034\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.689**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-0.561**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e-0.131\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.318\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.102\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.593\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.794\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCHILD score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.123\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.245\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.192\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.057\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.764\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMELD score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.482*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.149\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.433\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.186\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.324\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003eNS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003eTLC: Total leucocytic count, Hb: Hemoglobin, BUN: Blood urea nitrogen CR: Creatine, Na: Sodium, K: potassium, AST: Aspartate aminotransferase, ALT: Alanine transaminase, INR: International normalized ratio, and AFP: Alpha-feto protein\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSignificant Correlation between Neuropilin 1 level with BARCELONA score in group A (HCC) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (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 of Neuropilin 1 level with BARCELONA score in group A (HCC)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNeuropilin1 (ng/ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u003cp\u003eKruskal-Walli\u0026rsquo;s test\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMedian (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ek\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSig.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eBARCELONA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.94 (13.48\u0026ndash;19.63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e20.855\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eHS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.38 (26.63\u0026ndash;36.12)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48 (42.09\u0026ndash;49)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (50\u0026ndash;51)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe threshold for NRP1 concentration to distinguish between HCC and cirrhotic cases was determined to be \u0026gt;\u0026thinsp;10,7, with 96,67% sensitivity, 80% specificity, and AUC of 96,1%. For AFP, the threshold was \u0026gt;\u0026thinsp;5,6, with 80% sensitivity, 76,67% specificity, and an AUC of 82,1% (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\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\u003eComparative Diagnostic Accuracy of AFP and Neuropilin-1 for Detecting Hepatocellular Carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\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\u003eCut off point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAUC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eSensitivity\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eSpecificity\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e+PV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e-PV\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\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\u003eAFP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.821\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.700 to 0.908\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e76.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e77.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e79.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuropilin1 (ng/ml)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;10.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.961\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.877 to 0.994\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e96.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e82.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study included 60 subjects aged 28 to 91 years, recruited from Ain Shams University hospitals following the acquisition of written informed consent. The participants were categorized into (30 subjects/group): Group A (HCC): Cirrhotic patients with HCC and Group B (cirrhotic): cirrhotic patients, devoid of HCC.\u003c/p\u003e\u003cp\u003eOur research revealed a notable elevation in serum AFP levels among HCC patients, unlike cirrhotic patients. This observation aligned with several studies, including one \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e that recognizes elevated serum AFP as a diagnostic indicator for HCC when used in conjunction with triphasic CT abdomen or dynamic MRI. Furthermore, various guidelines suggest combining serum AFP with abdominal ultrasound for screening cirrhotic patients to enable early HCC detection. These outcomes reinforce the ongoing AFP reliability as an HCC indicator.\u003c/p\u003e\u003cp\u003eRegarding serum NRP1, a novel marker examined in this study, our results showed that the HCC group demonstrated significantly elevated NRP1 levels contrasted with the cirrhotic group (\u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.001), corroborating a previous study \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e, which demonstrated through cross-sectional analyses that HCC patients experienced significantly greater NRP1 levels than cirrhosis patients.\u003c/p\u003e\u003cp\u003eOur research revealed no statistically significant connection between NRP1, and platelet count or INR in both HCC and cirrhotic groups. This finding contradicts a previous study \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e, which reported a significant inverse correlation with platelet count and a positive correlation with INR. We found no statistically significant relationship between NRP1 and factors such as total leucocytic count (TLC), hemoglobin (Hb), and creatinine, aligned with earlier study \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e. Furthermore, our study manifested no statistical correlation between NRP1 and bilirubin, aligning with the findings in \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur research identified that NRP1 experienced a significant correlation with AST, ALT, AFP, and albumin, which agrees with the findings of \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e. We observed that MELD score had a positive and significant association with serum NRP1 levels, supporting the results of \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e. However, no significant connection between NRP1 levels and CHILD score was observed, which is consistent with the findings reported in \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOur outcomes revealed that the Barcelona score had a significant correlation with NRP1 levels, aligning with the results of \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e, which noted elevated serum NRP1 levels in tumor stages B/C per the Barcelona staging system.\u003c/p\u003e\u003cp\u003eIn our research, serum NRP1 manifested high sensitivity (96.67%) and specificity (80%) in detecting HCC, with an AUC of 0.961 at a threshold value\u0026thinsp;\u0026gt;\u0026thinsp;10.7 ng/ml. This compares to the findings of \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e, which reported a sensitivity 93.3% and specificity 80% (AUC\u0026thinsp;=\u0026thinsp;0.842,\u003c/p\u003e\u003cp\u003ethreshold value\u0026thinsp;=\u0026thinsp;4030 pg/ml).\u003c/p\u003e\u003cp\u003eHerein, we manifested that AFP exhibited a sensitivity (80%) and specificity (76.67%) in detecting HCC, indicating lower performance compared to NRP1. This supports the findings of \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e, which suggested that serum NRP1 serves as a superior diagnostic indicator compared to AFP, with an AUC of 0.971 for NRP1 versus 0.862 for AFP.\u003c/p\u003e\u003cp\u003eLimitations of our study encompass of a small patient sample size and lack of investigations to exclude other malignancies, such as mammograms or colonoscopies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSerum NRP1 levels were markedly greater in HCC patients and slightly elevated in liver cirrhotic patients but remained lower than those in the HCC group. NRP1 exhibited superior sensitivity and specificity compared to AFP. Integrating NRP1 into diagnostic protocols could improve HCC detection and facilitate early identification in surveillance programs, especially when used in conjunction with AFP.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAFP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAlpha-feto protein\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAspartate aminotransferase\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAlanine transaminase\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArea under curve\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCr\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecreatinine\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDb\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDirect bilirubin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHB\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ehemoglobin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHCC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHepatocellular carcinoma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eINR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInternational normalized ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eK\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003epotassium\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNRP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNeuropilin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003esodium\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTb\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003etotal bilirubin\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTLC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTotal leucocytic count\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted per Declaration of Helsinki (1975) and the Ethical Committee of the Faculty of Medicine at Ain Shams University, that approved the study prior to the study commencement. Each participant provided written consent.\u0026nbsp;\u003cstrong\u003eEthical number\u003c/strong\u003e: \u003cstrong\u003eFWA000017585\u003c/strong\u003e \u003cstrong\u003e(\u003c/strong\u003e\u003cstrong\u003eEthical approval date\u003c/strong\u003e :\u003cstrong\u003e17/1/2024\u003c/strong\u003e)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Publication Consent: Not Applicable.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding: No Fund\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eYang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol 16, 589\u0026ndash;604 (2019). \u003c/li\u003e\n\u003cli\u003eThokerunga E, Kisembo P, Fang Fang H, Wang Z, Zhang Y, Bongolo CC, et al. Serum Midkine for AFP-negative hepatocellular carcinoma diagnosis: a systematic review and meta-analysis. \u003cem\u003eEgypt Liver J\u003c/em\u003e 2023; 13:25.\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, et al. Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications. \u003cem\u003eClin Mol Hepatol\u003c/em\u003e 2023; 29:293.\u003c/li\u003e\n\u003cli\u003eBerg\u0026eacute; M, Allanic D, Bonnin P, de Montrion C, Richard J, Suc M, et al. Neuropilin-1 is upregulated in hepatocellular carcinoma and contributes to tumour growth and vascular remodelling. \u003cem\u003eJ Hepatol\u003c/em\u003e. 2011; 55(4):866-875. \u003c/li\u003e\n\u003cli\u003eJasirwan COM, Fahira A, Siregar L, Loho I. The alpha-fetoprotein serum is still reliable as a biomarker for the surveillance of hepatocellular carcinoma in Indonesia\u003cem\u003e. BMC Gastroenterol.\u003c/em\u003e 2020;20(1):215.\u003csup\u003e \u003c/sup\u003e\u003c/li\u003e\n\u003cli\u003eMostafa SE, Hany RE, Yasser MI, Ahmed EM. Neuropilin1 as a Diagnostic Marker for Hepatocellular Carcinoma\u003cem\u003e. Benha medical journal\u003c/em\u003e. 2022;39(2):515-28.\u003c/li\u003e\n\u003cli\u003eHoda AM and Dalia AM. The significance of neuropilin-1 for the diagnosis of hepatocellular carcinoma in Egyptian patients. Global scientific journal, 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, et al. Neuropilin 1 (NRP1) is a novel tumor marker in hepatocellular carcinoma. \u003cem\u003eClin Chim Acta\u003c/em\u003e. 2018; 485:158-65.\u003c/li\u003e\n\u003cli\u003eAbdel Ghafar MT, Elkhouly RA, Elnaggar MH, Mabrouk MM, Darwish SA, Younis RL, et al. Utility of serum neuropilin-1 and angiopoietin-2 as markers of hepatocellular carcinoma. \u003cem\u003eJ Investig Med\u003c/em\u003e. 2021;69(6):1222-29.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hepatocellular Carcinoma, Egyptian Cirrhotic, Serum Neuropilin 1, Diagnostic Biomarker","lastPublishedDoi":"10.21203/rs.3.rs-6959946/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6959946/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground/Aims: \u003c/strong\u003eIn recent decades, hepatocellular carcinoma has become the prevailing type of primary hepatic cancer, with its incidence rising dramatically. Many HCC patients are identified at an advanced, inoperable stage, limiting curative treatment options and resulting in poor survival rates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThis case control study encompassed 60 individuals, aged 18 and above, recruited from the hepatology and internal medicine clinics and hospital units between January 2024 and June 2024 at Ain Shams University Hospital.\u003cstrong\u003e \u003c/strong\u003eThe patients were classified as follows: Group 1 consisted of 30 HCC patients through alpha-fetoprotein testing and imaging. Group 2 comprised 30 cirrhotic patients, devoid of HCC, matched and categorized following the Child-Pugh scoring system\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e This investigation of Egyptian patients found that HCC typically emerges in the sixth decade of life and is often linked to liver cirrhosis. Patients with HCC exhibited significantly elevated serum alpha-fetoprotein (AFP) levels. Moreover, Neuropilin-1 (NRP1), a recently discovered biomarker, showed a substantial increase in HCC patients compared to cirrhosis patients. This elevation correlated strongly with liver function indicators (AST, ALT, AFP, albumin) and Barcelona and Child-Pugh scores. NRP1 demonstrated superior sensitivity (96.67%) and specificity (80%) in diagnosing HCC, unlike AFP, highlighting its capability as a more effective indicator for diagnosing HCC.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eSerum NRP1 levels were notably elevated in HCC patients. In contrast, cirrhotic patients showed only a slight increase in NRP1 levels compared to the HCC group.\u003c/p\u003e","manuscriptTitle":"The Utility of Serum Neuropilin 1 as a Diagnostic Biomarker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 08:30:32","doi":"10.21203/rs.3.rs-6959946/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":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-26T11:08:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-14 08:30:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6959946","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6959946","identity":"rs-6959946","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}