Diagnostic performance of serum origin recognition complex subunit 1 protein for hepatitis B virus-related hepatocellular carcinoma

doi:10.3748/wjg.v31.i44.112481

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Nov 28, 2025 (publication date) through Dec 1, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Nov 28, 2025; 31(44): 112481
Published online Nov 28, 2025. doi: 10.3748/wjg.v31.i44.112481

Diagnostic performance of serum origin recognition complex subunit 1 protein for hepatitis B virus-related hepatocellular carcinoma

Yan-Fei Feng, Tu-Mei Su, Bo-Bin Hu, Hang Wang, Qing-Mei Li, Qian-Bing Yin, Long Huang, Hong-Qian Liang, Ao-Li Ren, Ming-Hua Su, Jian-Ning Jiang

Yan-Fei Feng, Tu-Mei Su, Bo-Bin Hu, Hang Wang, Qing-Mei Li, Qian-Bing Yin, Long Huang, Hong-Qian Liang, Ao-Li Ren, Ming-Hua Su, Jian-Ning Jiang, Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China

Jian-Ning Jiang, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China

Co-first authors: Yan-Fei Feng and Tu-Mei Su.

Co-corresponding authors: Ming-Hua Su and Jian-Ning Jiang.

Author contributions: Feng YF and Su TM contributed equally to this work, and they are contributed equally to this manuscript and are co-first authors; Su MH and Jiang JN have made crucial and indispensable contributions towards the completion of the project and thus qualified as co-corresponding authors; Feng YF, Su TM, Hu BB, Wang H, Li QM, Yin QB, Huang L, Liang HQ, and Ren AL performed the research and analyzed the data; Feng YF and Su TM analyzed the data and wrote the manuscript; Su MH and Jiang JN designed and supervised the study; all authors read and approved the final version.

Supported by the National Natural Science Foundation of China, No. 81960115, No. 82160123, and No. 82260124; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, No. GKE-ZZ202107; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, No. GKE-ZZ202218; and Guangxi Science and Technology Program, No. AD25069077.

Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the First Affiliated Hospital of Guangxi Medical University (Approval No. 2025-E0523).

Informed consent statement: Consent was not obtained but the presented data are anonymized and risk of identification is low.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Jian-Ning Jiang, MD, PhD, Chief Physician, Professor, Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. gxjjianning@163.com

Received: July 29, 2025
Revised: September 13, 2025
Accepted: October 23, 2025
Published online: November 28, 2025
Processing time: 122 Days and 20.9 Hours

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with hepatitis B virus (HBV) infection serving as a significant etiological factor in endemic regions. Alpha-fetoprotein (AFP), the most commonly used biomarker, has limited sensitivity, particularly in AFP-negative HCC. Recent studies have identified origin recognition complex subunit 1 (ORC1) and extra spindle pole bodies-like 1 (ESPL1) as promising serum biomarkers, both linked to HBV DNA integration, a mechanism known to drive hepatocarcinogenesis.

AIM

To assess serum ORC1’s diagnostic value for HBV-HCC and its link to S gene integration.

METHODS

In this case-control study, 479 HBV-infected patients were enrolled, including 20 with HBV S gene integration, 47 with non-S gene integration, 162 with chronic hepatitis B, 154 with HBV-related cirrhosis, and 96 with HBV-HCC. The control group comprised 73 individuals: 29 with non-HBV-HCC and 44 healthy participants. Serum ORC1 and ESPL1 were measured by enzyme-linked immunosorbent assay. HBV integration sites were identified via whole-genome sequencing. Diagnostic performance was assessed using receiver operating characteristic analysis, including in AFP-negative patients.

RESULTS

HBV integration near the ORC1 locus (chromosome 1p32.3) was detected in 71.4% of HBV-HCC tissues. Serum ORC1 levels were significantly higher in HBV-infected patients than in non-HBV-infected controls (980.11 ng/L vs 746.82 ng/L, P < 0.05) and in HBV-HCC compared with non-HBV-HCC (1077.07 ng/L vs 749.54 ng/L, P < 0.05). Serum ORC1 and ESPL1 were elevated in HBV-HCC regardless of AFP status, and detected 64.8% and 73.2% of AFP-negative cases, respectively. The combined panel of ORC1 [Area under receiver operating characteristic curve (AUC) = 0.587], ESPL1 (AUC = 0.776), and AFP (AUC = 0.844) achieved an AUC of 0.887, significantly higher than any single marker (P < 0.05), with a sensitivity of 84.44%, specificity of 84.19%, and a negative predictive value of 94.91%.

CONCLUSION

Serum ORC1, driven by HBV integration, is a promising biomarker especially for AFP-negative HBV-HCC. Its combination with ESPL1 and AFP significantly improves early detection.

Keywords: Hepatocellular carcinoma; Hepatitis B virus; Origin recognition complex subunit 1; Diagnostic biomarker; Alpha-fetoprotein-negative; Enzyme-linked immunosorbent assay

Core Tip: This study identifies serum origin recognition complex subunit 1 (ORC1) as a novel diagnostic biomarker for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). ORC1 levels were markedly elevated in HBV-HCC patients, especially those negative for alpha-fetoprotein. Mechanistically, recurrent HBV integration near the ORC1 locus appears to drive its aberrant expression, contributing to hepatocarcinogenesis. These findings highlight ORC1 as a promising biomarker that complements alpha-fetoprotein, substantially improving early detection accuracy and offering strong potential for clinical translation in HBV-HCC screening.