{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:12:51Z","timestamp":1788577971416,"version":"build-2803163510"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Primary liver cancer (PLC) is a biologically heterogeneous group of malignancies dominated by hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and a smaller subset of combined hepatocellular\u2010cholangiocarcinoma (cHCC\u2010CCA), and its clinical burden remains high because current diagnostic and prognostic tools do not adequately capture molecular diversity. Conventional imaging, serum markers, and histopathological assessment remain insufficient for precise early diagnosis, subtype\u2010resolved classification, and outcome stratification, while tissue and liquid biopsy approaches have expanded the range of analytes available for clinical assessment. Recent studies have identified candidate biomarker signatures across genomic, epigenomic, transcriptomic, proteomic, metabolomic, and circulating layers, suggesting that integrated multi\u2010omics profiling may better represent tumor lineage, clonal evolution, immune context, and therapeutic vulnerability than isolated molecular readouts. However, these layers are not equally mature for clinical use: genomic testing is closest to routine therapeutic application in iCCA, plasma methylation assays are advancing for HCC surveillance augmentation, and many proteomic or metabolomic panels remain validation\u2010stage tools. Their clinical value remains constrained by sampling bias, biospecimen\u2010dependent signal loss, assay standardization, cost, and the need for prospective validation across clinically diverse populations. This narrative review critically synthesizes current evidence on multi\u2010omics biomarker signatures for precision diagnosis and prognosis in primary liver cancer and argues that clinically useful signatures should be question\u2010specific, stage\u2010aware, and specimen\u2010aware rather than universal multi\u2010analyte panels.<\/jats:p>","DOI":"10.1002\/biof.70136","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:45:56Z","timestamp":1788576356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review"],"prefix":"10.1002","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5465-3301","authenticated-orcid":false,"given":"Ke","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Oncology Chongqing General Hospital, Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology Chongqing General Hospital, Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4347-9875","authenticated-orcid":false,"given":"Yuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Oncology Chongqing General Hospital, Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Oncology Chongqing General Hospital, Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Oncology Chongqing General Hospital, Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"3","key":"e_1_2_15_2_1","first-page":"229","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray F.","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"issue":"6","key":"e_1_2_15_3_1","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.jhep.2022.08.021","article-title":"Global Burden of Primary Liver Cancer in 2020 and Predictions to 2040","volume":"77","author":"Rumgay H.","year":"2022","journal-title":"Journal of Hepatology"},{"issue":"1","key":"e_1_2_15_4_1","doi-asserted-by":"crossref","first-page":"e312","DOI":"10.71321\/e37ss652","article-title":"The Recent Changing Global Landscape of Cancer","volume":"2","author":"Karsidag I.","year":"2025","journal-title":"Life Conflux"},{"issue":"1","key":"e_1_2_15_5_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/poh2.70033","article-title":"Primary Liver Cancer Trends Worldwide and in China: Analysis of GLOBOCAN 2022 Data and Disease Management Implications","volume":"5","author":"Yan J.","year":"2026","journal-title":"Portal Hypertension & Cirrhosis"},{"issue":"5","key":"e_1_2_15_6_1","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.jhep.2021.01.035","article-title":"Combined Hepatocellular\u2010Cholangiocarcinoma: An Update","volume":"74","author":"Beaufr\u00e8re A.","year":"2021","journal-title":"Journal of Hepatology"},{"issue":"8","key":"e_1_2_15_7_1","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.molmed.2025.01.008","article-title":"Molecular Subtypes of Intrahepatic Cholangiocarcinoma","volume":"31","author":"De Santis A.","year":"2025","journal-title":"Trends in Molecular Medicine"},{"key":"e_1_2_15_8_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. 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