{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:00:12Z","timestamp":1793037612020,"version":"4.5.0"},"reference-count":38,"publisher":"Baishideng Publishing Group Inc.","issue":"44","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["World J Gastroenterol"],"abstract":"<jats:p>BACKGROUND<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>AIM<\/jats:p>\n                  <jats:p>To assess serum ORC1\u2019s diagnostic value for HBV-HCC and its link to S  gene integration.<\/jats:p>\n                  <jats:p>METHODS<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n                  <jats:p>RESULTS<\/jats:p>\n                  <jats:p>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  &lt; 0.05) and in HBV-HCC compared with non-HBV-HCC (1077.07 ng\/L vs  749.54 ng\/L, P  &lt; 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  &lt; 0.05), with a sensitivity of 84.44%, specificity of 84.19%, and a negative predictive value of 94.91%.<\/jats:p>\n                  <jats:p>CONCLUSION<\/jats:p>\n                  <jats:p>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.<\/jats:p>","DOI":"10.3748\/wjg.v31.i44.112481","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T09:20:43Z","timestamp":1764235243000},"source":"Crossref","is-referenced-by-count":3,"title":["Diagnostic performance of serum origin recognition complex subunit 1 protein for hepatitis B virus-related hepatocellular 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