{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:01:27Z","timestamp":1789974087887,"version":"4.0.1"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515010135"],"award-info":[{"award-number":["2023A1515010135"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Surgical Oncology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) remains a global health challenge with high recurrence rates despite surgical resection. Current biomarkers lack sensitivity for early relapse detection, underscoring the need for novel strategies. Circulating tumor DNA (ctDNA) has emerged as a promising tool for minimal residual disease (MRD) monitoring, yet its prognostic and therapeutic implications in HCC remain underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study enrolled 23 HCC patients undergoing R0 resection. Preoperative and serial postoperative plasma samples were analyzed using a 425\u2010gene next\u2010generation sequencing panel to detect MRD. Tissue\u2010plasma mutation concordance, recurrence risk stratification, and therapeutic applications were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MRD positivity at postoperative Day 7 predicted significantly shorter disease\u2010free survival (DFS: 3.06 vs. not reached;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0027). Dynamic monitoring revealed three recurrence risk groups: persistently MRD\u2010positive (highest risk, HR 4.12;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), MRD\u2010negative\u2010to\u2010positive (intermediate), and continuously negative (lowest). ctDNA detected recurrence 16 weeks earlier than imaging (81.8% sensitivity, 100% specificity). High tissue\u2010plasma mutation concordance (84.6%) confirmed ctDNA's biological relevance, with TP53 (60.9% tissue\/70% plasma) and CTNNB1 (17.4%\/25%) as predominant drivers. ASXL1 mutations (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025) and microvascular invasion (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) independently predicted poor DFS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Dynamic ctDNA analysis improves postoperative HCC management through early recurrence prediction and precision therapy guidance. High mutation concordance validates its role in reflecting tumor heterogeneity, while MRD trajectory stratification enables personalized surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jso.70405","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:13:07Z","timestamp":1789971187000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic ctDNA Monitoring Predicts Recurrence and Guides Therapy in Postoperative Hepatocellular Carcinoma"],"prefix":"10.1002","author":[{"given":"Jianliang","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery The Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6579-5559","authenticated-orcid":false,"given":"Mingxing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-6179","authenticated-orcid":false,"given":"Yanjie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1545-2857","authenticated-orcid":false,"given":"Jiehui","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery The Third Affiliated Hospital, Sun Yat\u2010sen University Guangzhou Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"issue":"10360","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/S0140-6736(22)01200-4","article-title":"Hepatocellular Carcinoma","volume":"400","author":"Vogel A.","year":"2022","journal-title":"Lancet"},{"issue":"1","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41572-021-00245-6","article-title":"Hepatocellular Carcinoma","volume":"7","year":"2021","journal-title":"Nature Reviews Disease Primers"},{"issue":"4","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1001\/jamasurg.2022.7989","article-title":"Management of Hepatocellular Carcinoma: A Review","volume":"158","author":"Brown Z. J.","year":"2023","journal-title":"JAMA Surgery"},{"issue":"5","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.bpg.2014.07.018","article-title":"Hepatocellular Carcinoma Tumour Markers: Current Role and Expectations","volume":"28","author":"Rich N.","year":"2014","journal-title":"Best Practice & Research Clinical Gastroenterology"},{"issue":"2","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1053\/j.gastro.2009.10.031","article-title":"Des\u2010\u03b3\u2010Carboxy Prothrombin and \u03b1\u2010Fetoprotein as Biomarkers for the Early Detection of Hepatocellular Carcinoma","volume":"138","author":"Lok A. S.","year":"2010","journal-title":"Gastroenterology"},{"issue":"13","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.7150\/jca.15823","article-title":"Detecting Circulating Tumor DNA in Hepatocellular Carcinoma Patients Using Droplet Digital PCR is Feasible and Reflects Intratumoral Heterogeneity","volume":"7","author":"Huang A.","year":"2016","journal-title":"Journal of Cancer"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13578-016-0100-z","article-title":"Circulating Tumor DNA in Hepatocellular Carcinoma: Trends and Challenges","volume":"6","author":"Tang J. C.","year":"2016","journal-title":"Cell & Bioscience"},{"issue":"5","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jcmgh.2015.06.009","article-title":"Circulating Tumor DNA Analysis for Liver Cancers and Its Usefulness as a Liquid Biopsy","volume":"1","author":"Ono A.","year":"2015","journal-title":"Cellular and Molecular Gastroenterology and Hepatology"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejca.2019.04.014","article-title":"Identification of Mutations in Circulating Cell\u2010Free Tumour DNA as a Biomarker in Hepatocellular Carcinoma","volume":"116","author":"Howell J.","year":"2019","journal-title":"European Journal of Cancer"},{"issue":"17","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"5284","DOI":"10.1158\/1078-0432.CCR-18-3477","article-title":"Comprehensive Liquid Profiling of Circulating Tumor DNA and Protein Biomarkers in Long\u2010Term Follow\u2010Up Patients With Hepatocellular Carcinoma","volume":"25","author":"Cai Z.","year":"2019","journal-title":"Clinical Cancer Research"},{"issue":"1","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"6770","DOI":"10.1038\/s41467-021-27022-z","article-title":"Dynamic Recurrence Risk and Adjuvant Chemotherapy Benefit Prediction by ctDNA in Resected NSCLC","volume":"12","author":"Qiu B.","year":"2021","journal-title":"Nature Communications"},{"issue":"5","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1245\/s10434-019-07227-9","article-title":"Prognostic and Therapeutic Implications of Microvascular Invasion in Hepatocellular Carcinoma","volume":"26","author":"Erstad D. J.","year":"2019","journal-title":"Annals of Surgical Oncology"},{"issue":"4","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/cac2.12414","article-title":"Cancer\u2010Associated Fibroblast\u2010Derived Secreted Phosphoprotein 1 Contributes to Resistance of Hepatocellular Carcinoma to Sorafenib and Lenvatinib","volume":"43","author":"Eun J. W.","year":"2023","journal-title":"Cancer Communications"},{"issue":"3","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/s41591-023-02786-7","article-title":"Adjuvant Sintilimab in Resected High\u2010Risk Hepatocellular Carcinoma: A Randomized, Controlled, Phase 2 Trial","volume":"30","author":"Wang K.","year":"2024","journal-title":"Nature Medicine"},{"issue":"6","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1007\/s40265-021-01503-3","article-title":"Entrectinib: A Review in NTRK+ Solid Tumours and ROS1+ NSCLC","volume":"81","author":"Frampton J. E.","year":"2021","journal-title":"Drugs"},{"issue":"1","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s12943-019-1043-x","article-title":"Liquid Biopsy in Hepatocellular Carcinoma: Circulating Tumor Cells and Circulating Tumor Dna","volume":"18","author":"Ye Q.","year":"2019","journal-title":"Molecular cancer"},{"issue":"1","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/s41591-022-02115-4","article-title":"Molecular Residual Disease and Efficacy of Adjuvant Chemotherapy in Patients With Colorectal Cancer","volume":"29","author":"Kotani D.","year":"2023","journal-title":"Nature Medicine"},{"issue":"22","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"4540","DOI":"10.1158\/1078-0432.CCR-23-0757","article-title":"Molecular Residual Disease in Breast Cancer: Detection and Therapeutic Interception","volume":"29","author":"Medford A. J.","year":"2023","journal-title":"Clinical Cancer Research"},{"issue":"5","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1097\/SLA.0000000000000710","article-title":"Recurrence of Hepatocellular Cancer After Resection: Patterns, Treatments, and Prognosis","volume":"261","author":"Tabrizian P.","year":"2015","journal-title":"Annals of Surgery"},{"issue":"1","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s12943-024-02101-z","article-title":"Biomarkers for Diagnosis and Therapeutic Options in Hepatocellular Carcinoma","volume":"23","author":"Chan Y. T.","year":"2024","journal-title":"Molecular cancer"},{"issue":"4","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1007\/s12072-022-10348-1","article-title":"Preoperative Serum Ctdna Predicts Early Hepatocellular Carcinoma Recurrence and Response to Systemic Therapies","volume":"16","author":"Fu Y.","year":"2022","journal-title":"Hepatology International"},{"issue":"4","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2022-004656","article-title":"Efficacy and Safety of Camrelizumab Plus Apatinib During the Perioperative Period in Resectable Hepatocellular Carcinoma: A Single\u2010Arm, Open Label, Phase II Clinical Trial","volume":"10","author":"Xia Y.","year":"2022","journal-title":"Journal for Immunotherapy of Cancer"},{"issue":"2","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.cell.2019.08.052","article-title":"Integrated Proteogenomic Characterization of HBV\u2010Related Hepatocellular Carcinoma","volume":"179","author":"Gao Q.","year":"2019","journal-title":"Cell"},{"issue":"5","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/ng.3252","article-title":"Exome Sequencing of Hepatocellular Carcinomas Identifies New Mutational Signatures and Potential Therapeutic Targets","volume":"47","author":"Schulze K.","year":"2015","journal-title":"Nature Genetics"},{"issue":"20","key":"e_1_2_10_26_1","doi-asserted-by":"crossref","DOI":"10.1111\/jcmm.70083","article-title":"Integrative Transcriptome Analysis Identifies a Crotonylation Gene Signature for Predicting Prognosis and Drug Sensitivity in Hepatocellular Carcinoma","volume":"28","author":"Yang B.","year":"2024","journal-title":"Journal of Cellular and Molecular Medicine"},{"key":"e_1_2_10_27_1","doi-asserted-by":"crossref","DOI":"10.1177\/11795549231180840","article-title":"The Genomic and Proteomic Profiles of NTRK Genes and Trk Receptors in Liver Hepatocellular Carcinoma","volume":"17","author":"Wang H.","year":"2023","journal-title":"Clinical Medicine Insights: Oncology"},{"issue":"4","key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1158\/1078-0432.CCR-20-2771","article-title":"FDA Approval Summary: Entrectinib for the Treatment of NTRK Gene Fusion Solid Tumors","volume":"27","author":"Marcus L.","year":"2021","journal-title":"Clinical Cancer Research"},{"issue":"8","key":"e_1_2_10_29_1","doi-asserted-by":"crossref","first-page":"viii23","DOI":"10.1093\/annonc\/mdz282","article-title":"TRK Inhibitors in TRK Fusion\u2010Positive Cancers","volume":"30","author":"Drilon A.","year":"2019","journal-title":"Annals of Oncology"},{"issue":"20","key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma","volume":"382","author":"Finn R. S.","year":"2020","journal-title":"New England Journal of Medicine"},{"issue":"1","key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrclinonc.2016.96","article-title":"Combine and Conquer: Challenges for Targeted Therapy Combinations in Early Phase Trials","volume":"14","author":"Lopez J. S.","year":"2017","journal-title":"Nature Reviews Clinical Oncology"}],"container-title":["Journal of Surgical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jso.70405","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jso.70405","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jso.70405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:13:12Z","timestamp":1789971192000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jso.70405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":30,"alternative-id":["10.1002\/jso.70405"],"URL":"https:\/\/doi.org\/10.1002\/jso.70405","archive":["Portico"],"relation":{},"ISSN":["0022-4790","1096-9098"],"issn-type":[{"value":"0022-4790","type":"print"},{"value":"1096-9098","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]},"assertion":[{"value":"2026-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jso.70405"}}