{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:09:21Z","timestamp":1777680561581,"version":"3.51.4"},"reference-count":143,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The key scientific research project plan of Henan Province","award":["24A330001"],"award-info":[{"award-number":["24A330001"]}]},{"name":"The program for science and technology development in Henan Province","award":["252102310322"],"award-info":[{"award-number":["252102310322"]}]},{"name":"The program for science and technology development in Henan Province","award":["252102311118"],"award-info":[{"award-number":["252102311118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Hepatocellular carcinoma (HCC) is an important cause of cancer-related death. Due to the lack of typical clinical symptoms in early-stage HCC, most HCC patients are diagnosed at an advanced stage and have lost the opportunity of surgery, which results in a poor prognosis. Therefore, early detection and timely intervention are the most effective methods to reduce the mortality of HCC. Blood flows through different organs and tissues, and there are abundant tumor biomarkers in blood, which can provide real-time information for the early diagnosis and prognostic prediction of HCC, so blood tumor biomarkers have become an effective supplement to imaging technology. As the most ideal biomarkers for disease diagnosis, serum and plasma proteins have been the main focus for biomarker development. In this review, we summarized the research progress of potential blood protein biomarkers (tumor-associated antigens and tumor-associated autoantibodies) in HCC and discussed their obstacles in clinical translation.<\/jats:p>","DOI":"10.7717\/peerj.21196","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:36:32Z","timestamp":1777451792000},"page":"e21196","source":"Crossref","is-referenced-by-count":0,"title":["Blood protein biomarkers in hepatocellular carcinoma: progress and challenges"],"prefix":"10.7717","volume":"14","author":[{"given":"Lu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Public Health and Epidemiology, School of Basic Medical Sciences, Henan University, Kaifeng, China"},{"name":"Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, School of Basic Medical Sciences, Henan University, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, School of Basic Medical Sciences, Henan University, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, School of Basic Medical Sciences, Henan University, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, School of Basic Medical Sciences, Henan University, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology, Kaifeng Central Hospital, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yange","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Genetics, School of Basic Medical Sciences, Henan University, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peijie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Kaifeng Central Hospital, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangqian","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, School of Basic Medical Sciences, Henan University, Kaifeng, China"},{"name":"Henan Provincial Engineering Center for Tumor Molecular Medicine, Kaifeng, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"10.7717\/peerj.21196\/ref-1","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1136\/jim-2020-001744","article-title":"Utility of serum neuropilin-1 and angiopoietin-2 as markers of hepatocellular carcinoma","volume":"69","author":"Abdel\u00a0Ghafar","year":"2021","journal-title":"Journal of Investigative Medicine"},{"key":"10.7717\/peerj.21196\/ref-2","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1080\/1354750X.2016.1252966","article-title":"Identification of circulating protein biomarkers in patients with hepatocellular carcinoma concomitantly infected with chronic hepatitis C virus","volume":"22","author":"Abdel\u00a0Wahab","year":"2017","journal-title":"Biomarkers"},{"key":"10.7717\/peerj.21196\/ref-3","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ajg.2020.04.017","article-title":"Talin-1; other than a potential marker for hepatocellular carcinoma diagnosis","volume":"21","author":"Aboelfotoh","year":"2020","journal-title":"Arab Journal of Gastroenterology"},{"key":"10.7717\/peerj.21196\/ref-4","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1111\/jgh.14535","article-title":"Monitoring serum proangiogenic cytokines from hepatocellular carcinoma patients treated with sorafenib","volume":"34","author":"Adachi","year":"2019","journal-title":"Journal of Gastroenterology and Hepatology"},{"key":"10.7717\/peerj.21196\/ref-5","doi-asserted-by":"publisher","first-page":"376","DOI":"10.3390\/cancers17030376","article-title":"Personalized immunity: neoantigen-based vaccines revolutionizing hepatocellular carcinoma treatment","volume":"17","author":"Aggeletopoulou","year":"2025","journal-title":"Cancer"},{"key":"10.7717\/peerj.21196\/ref-6","doi-asserted-by":"publisher","first-page":"2493457","DOI":"10.1080\/20450923.2025.2493457","article-title":"Advancing precision medicine in hepatocellular carcinoma: current challenges and future directions in liquid biopsy, immune microenvironment, single nucleotide polymorphisms, and conversion therapy","volume":"12","author":"Akabane","year":"2025","journal-title":"Hepatic Oncology"},{"key":"10.7717\/peerj.21196\/ref-7","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00281-022-00966-0","article-title":"Tumor microenvironment antigens","volume":"45","author":"Andersen","year":"2023","journal-title":"Seminars in Immunopathology"},{"key":"10.7717\/peerj.21196\/ref-8","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/hep.29291","article-title":"Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma","volume":"66","author":"Arbelaiz","year":"2017","journal-title":"Hepatology"},{"key":"10.7717\/peerj.21196\/ref-9","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1016\/j.eururo.2007.09.036","article-title":"Challenges of cancer biomarker profiling","volume":"52","author":"Bensalah","year":"2007","journal-title":"European Urology"},{"key":"10.7717\/peerj.21196\/ref-10","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA: A Cancer Journal for Clinicians"},{"key":"10.7717\/peerj.21196\/ref-11","doi-asserted-by":"publisher","first-page":"eadn3628","DOI":"10.1126\/sciadv.adn3628","article-title":"Microproteins encoded by noncanonical ORFs are a major source of tumor-specific antigens in a liver cancer patient meta-cohort","volume":"10","author":"Camarena","year":"2024","journal-title":"Science Advances"},{"key":"10.7717\/peerj.21196\/ref-12","doi-asserted-by":"publisher","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","year":"2024","journal-title":"Molecular Cancer"},{"key":"10.7717\/peerj.21196\/ref-13","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/s00262-018-2271-4","article-title":"The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma","volume":"68","author":"Chang","year":"2019","journal-title":"Cancer Immunology Immunotherapy"},{"key":"10.7717\/peerj.21196\/ref-14","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.2147\/JHC.S325629","article-title":"Serum KLKB1 as a potential prognostic biomarker for hepatocellular carcinoma based on data-independent acquisition and parallel reaction monitoring","volume":"8","author":"Che","year":"2021","journal-title":"Journal of Hepatocellular Carcinoma"},{"key":"10.7717\/peerj.21196\/ref-15","doi-asserted-by":"publisher","first-page":"2032056","DOI":"10.1155\/2020\/2032056","article-title":"Identification of serum CMTM2 as a potential biomarker for HBV-related disorders","volume":"2020","author":"Chen","year":"2020","journal-title":"Disease Markers"},{"key":"10.7717\/peerj.21196\/ref-16","doi-asserted-by":"publisher","first-page":"102638","DOI":"10.1016\/j.ebiom.2020.102638","article-title":"A panel of five plasma proteins for the early diagnosis of hepatitis B virus-related hepatocellular carcinoma in individuals at risk","volume":"52","author":"Cheng","year":"2020","journal-title":"EBioMedicine"},{"key":"10.7717\/peerj.21196\/ref-17","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.31557\/APJCP.2022.23.6.2017","article-title":"Targeted proteins reveal cathepsin D as a novel biomarker in differentiating hepatocellular carcinoma from cirrhosis and other liver cancers","volume":"23","author":"Chuaypen","year":"2022","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"10.7717\/peerj.21196\/ref-18","doi-asserted-by":"publisher","first-page":"e12419","DOI":"10.1371\/journal.pone.0012419","article-title":"Linkage specific fucosylation of alpha-1-antitrypsin in liver cirrhosis and cancer patients: implications for a biomarker of hepatocellular carcinoma","volume":"5","author":"Comunale","year":"2010","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.21196\/ref-19","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1002\/ijc.28953","article-title":"Osteopontin and latent-TGF\u03b2 binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma","volume":"136","author":"Da\u00a0Costa","year":"2015","journal-title":"International Journal of Cancer"},{"key":"10.7717\/peerj.21196\/ref-20","doi-asserted-by":"publisher","first-page":"20276","DOI":"10.1038\/s41598-020-77332-3","article-title":"Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection","volume":"10","author":"Deng","year":"2020","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.21196\/ref-21","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1007\/s12029-019-00323-9","article-title":"May neutrophil gelatinase-associated lipocalin (NGAL) level predict mortality in patients with hepatocellular carcinoma (HCC)?","volume":"51","author":"Dertli","year":"2020","journal-title":"Journal of Gastrointestinal Cancer"},{"key":"10.7717\/peerj.21196\/ref-22","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1002\/hep.32740","article-title":"The liver cancer immune microenvironment: therapeutic implications for hepatocellular carcinoma","volume":"77","author":"Donne","year":"2023","journal-title":"Hepatology"},{"key":"10.7717\/peerj.21196\/ref-23","doi-asserted-by":"publisher","first-page":"6607","DOI":"10.1007\/s13277-015-4423-x","article-title":"Elevated serum soluble CD14 levels in chronic HBV infection are significantly associated with HBV-related hepatocellular carcinoma","volume":"37","author":"Dou","year":"2016","journal-title":"Tumour Biology"},{"key":"10.7717\/peerj.21196\/ref-24","doi-asserted-by":"publisher","first-page":"15552","DOI":"10.1038\/s41598-020-72510-9","article-title":"Quantitative proteomics identifies a plasma multi-protein model for detection of hepatocellular carcinoma","volume":"10","author":"Du","year":"2020","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.21196\/ref-25","doi-asserted-by":"publisher","first-page":"7758735","DOI":"10.1155\/2022\/7758735","article-title":"Identification of CCL20 and LCN2 as efficient serological tools for detection of hepatocellular carcinoma","volume":"2022","author":"Du","year":"2022","journal-title":"Disease Markers"},{"key":"10.7717\/peerj.21196\/ref-26","doi-asserted-by":"publisher","first-page":"971","DOI":"10.3389\/fonc.2020.00971","article-title":"ULBP1 is elevated in human hepatocellular carcinoma and predicts outcome","volume":"10","author":"Easom","year":"2020","journal-title":"Frontiers in Oncology"},{"key":"10.7717\/peerj.21196\/ref-27","doi-asserted-by":"publisher","first-page":"e25112","DOI":"10.1097\/MD.0000000000025112","article-title":"Serum midkine is a more sensitive predictor for hepatocellular carcinoma than Dickkopf-1 and alpha-L-fucosidase in cirrhotic HCV patients","volume":"100","author":"El-Shayeb","year":"2021","journal-title":"Medicine"},{"key":"10.7717\/peerj.21196\/ref-28","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s12029-020-00389-w","article-title":"Prognostic significance of VEGF and HIF-1\u03b1 in hepatocellular carcinoma patients receiving sorafenib versus metformin sorafenib combination","volume":"52","author":"El\u00a0Shorbagy","year":"2021","journal-title":"Journal of Gastrointestinal Cancer"},{"key":"10.7717\/peerj.21196\/ref-29","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1515\/cclm-2022-1090","article-title":"Clinical usefulness of circulating tumor markers","volume":"61","author":"Filella","year":"2022","journal-title":"Clinical Chemistry and Laboratory Medicine"},{"key":"10.7717\/peerj.21196\/ref-30","doi-asserted-by":"publisher","first-page":"6105","DOI":"10.1038\/s41388-018-0391-0","article-title":"Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer","volume":"37","author":"Fu","year":"2018","journal-title":"Oncogene"},{"key":"10.7717\/peerj.21196\/ref-31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/bs.acr.2020.10.002","article-title":"Signaling pathways in hepatocellular carcinoma","volume":"149","author":"Garcia-Lezana","year":"2021","journal-title":"Advances in Cancer Research"},{"key":"10.7717\/peerj.21196\/ref-32","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.3892\/or.2018.6922","article-title":"Early decrease in serum amphiregulin or vascular endothelial growth factor levels predicts sorafenib efficacy in hepatocellular carcinoma","volume":"41","author":"Godin","year":"2019","journal-title":"Oncology Reports"},{"key":"10.7717\/peerj.21196\/ref-33","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.mad.2006.11.021","article-title":"Protein microarray technology","volume":"128","author":"Hall","year":"2007","journal-title":"Mechanisms of Ageing and Development"},{"key":"10.7717\/peerj.21196\/ref-34","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.cell.2018.02.061","article-title":"Tumor-induced generation of splenic erythroblast-like Ter-cells promotes tumor progression","volume":"173","author":"Han","year":"2018","journal-title":"Cell"},{"key":"10.7717\/peerj.21196\/ref-35","doi-asserted-by":"publisher","first-page":"100872","DOI":"10.1016\/j.mcpro.2024.100872","article-title":"Screening of cancer-specific biomarkers for hepatitis B-related hepatocellular carcinoma based on a proteome microarray","volume":"23","author":"Hao","year":"2024","journal-title":"Molecular Cell Proteomics"},{"key":"10.7717\/peerj.21196\/ref-36","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1200\/JCO.20.01572","article-title":"Defining clinical utility of tumor biomarker tests: a clinician\u2019s viewpoint","volume":"39","author":"Hayes","year":"2021","journal-title":"Journal of Clinical Oncology"},{"key":"10.7717\/peerj.21196\/ref-37","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.1093\/carcin\/bgv081","article-title":"Hepatocellular carcinoma-derived exosomes promote motility of immortalized hepatocyte through transfer of oncogenic proteins and RNAs","volume":"36","author":"He","year":"2015","journal-title":"Carcinogenesis"},{"key":"10.7717\/peerj.21196\/ref-38","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1136\/gut.2008.157016","article-title":"Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis","volume":"58","author":"Henry","year":"2009","journal-title":"Gut"},{"key":"10.7717\/peerj.21196\/ref-39","doi-asserted-by":"publisher","first-page":"11059","DOI":"10.1038\/s41598-019-47365-4","article-title":"Serum anti-EIF3A autoantibody as a potential diagnostic marker for hepatocellular carcinoma","volume":"9","author":"Heo","year":"2019","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.21196\/ref-40","doi-asserted-by":"publisher","first-page":"9718","DOI":"10.3390\/ijms21249718","article-title":"Cyclic peptide mimotopes for the detection of serum anti-ATIC autoantibody biomarker in hepato-cellular carcinoma","volume":"21","author":"Heo","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.21196\/ref-41","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.3892\/ijo_00000631","article-title":"Identification of autoantibody against fatty acid synthase in hepatocellular carcinoma mouse model and its application to diagnosis of HCC","volume":"36","author":"Heo","year":"2010","journal-title":"International Journal of Oncology"},{"key":"10.7717\/peerj.21196\/ref-42","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.4254\/wjh.v7.i11.1581","article-title":"Autoantibodies against tumor-associated antigens for detection of hepatocellular carcinoma","volume":"7","author":"Hong","year":"2015","journal-title":"World Journal of Hepatology"},{"key":"10.7717\/peerj.21196\/ref-43","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1186\/s12967-021-03038-3","article-title":"Use of proteomics to identify mechanisms of hepatocellular carcinoma with the CYP2D6*10 polymorphism and identification of ANGPTL6 as a new diagnostic and prognostic biomarker","volume":"19","author":"Hu","year":"2021","journal-title":"Journal of Translational Medicine"},{"key":"10.7717\/peerj.21196\/ref-44","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/wsbm.118","article-title":"Functional protein microarray technology","volume":"3","author":"Hu","year":"2011","journal-title":"Wiley Interdisciplinary Reviews-Systems Biology and Medicine"},{"key":"10.7717\/peerj.21196\/ref-45","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1021\/acs.jproteome.3c00813","article-title":"Proteomic analysis identifies GSN as a noninvasive circulating serum biomarker for predicting early recurrence of hepatocellular carcinoma","volume":"23","author":"Hu","year":"2024","journal-title":"Journal of Proteome Research"},{"key":"10.7717\/peerj.21196\/ref-46","doi-asserted-by":"publisher","first-page":"215886","DOI":"10.1016\/j.canlet.2022.215886","article-title":"Blood protein biomarkers in lung cancer","volume":"551","author":"Huang","year":"2022","journal-title":"Cancer Letters"},{"key":"10.7717\/peerj.21196\/ref-47","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1007\/s12032-012-0257-1","article-title":"MAGE-4 gene m-RNA and TGF in blood as potential biochemical markers for HCC in HCV-infected patients","volume":"29","author":"Hussein","year":"2012","journal-title":"Medical Oncology"},{"key":"10.7717\/peerj.21196\/ref-48","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1186\/s12967-018-1546-z","article-title":"Identification of anti-SF3B1 autoantibody as a diagnostic marker in patients with hepatocellular carcinoma","volume":"16","author":"Hwang","year":"2018","journal-title":"Journal of Translational Medicine"},{"key":"10.7717\/peerj.21196\/ref-49","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1177\/172460080301800311","article-title":"Are 90K\/MAC-2BP serum levels correlated with poor prognosis in HCC patients? Preliminary results","volume":"18","author":"Iacovazzi","year":"2003","journal-title":"International Journal of Biological Markers"},{"key":"10.7717\/peerj.21196\/ref-50","doi-asserted-by":"publisher","first-page":"595","DOI":"10.33594\/000000042","article-title":"Analysis of lamin B1, vimentin and anti-ku86 as prospective biomarkers of hepatocellular carcinoma in patients with hepatitis C virus infection","volume":"52","author":"Idriss","year":"2019","journal-title":"Cellular Physiology and Biochemistry"},{"key":"10.7717\/peerj.21196\/ref-51","doi-asserted-by":"publisher","first-page":"2204","DOI":"10.1158\/1055-9965.EPI-11-0464","article-title":"Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C","volume":"20","author":"Ikeda","year":"2011","journal-title":"Cancer Epidemiology, Biomarkers & Prevention"},{"key":"10.7717\/peerj.21196\/ref-52","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1080\/00365513.2017.1286684","article-title":"Evaluation of prothrombin induced by vitamin K absence, macrophage migration inhibitory factor and Golgi protein-73 versus alpha fetoprotein for hepatocellular carcinoma diagnosis and surveillance","volume":"77","author":"Ismail","year":"2017","journal-title":"Scandinavian Journal of Clinical and Laboratory Investigation"},{"key":"10.7717\/peerj.21196\/ref-53","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.7314\/apjcp.2015.16.4.1657","article-title":"Plasma nuclear factor kappa B and serum peroxiredoxin 3 in early diagnosis of hepatocellular carcinoma","volume":"16","author":"Ismail","year":"2015","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"10.7717\/peerj.21196\/ref-54","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1016\/j.cyto.2012.07.017","article-title":"Serum interleukin-6 and C-reactive protein as a prognostic indicator in hepatocellular carcinoma","volume":"60","author":"Jang","year":"2012","journal-title":"Cytokine"},{"key":"10.7717\/peerj.21196\/ref-55","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1007\/s12253-019-00752-8","article-title":"Differential expression and diagnostic significance of pre-albumin, fibrinogen combined with D-Dimer in AFP-negative hepatocellular carcinoma","volume":"26","author":"Jing","year":"2020","journal-title":"Pathology Oncology Research"},{"key":"10.7717\/peerj.21196\/ref-56","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1111\/cas.13261","article-title":"Serum monomeric laminin-\u03b32 as a novel biomarker for hepatocellular carcinoma","volume":"108","author":"Kiyokawa","year":"2017","journal-title":"Cancer Science"},{"key":"10.7717\/peerj.21196\/ref-57","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1111\/jgh.13148","article-title":"Circulating CD147 predicts mortality in advanced hepatocellular carcinoma","volume":"31","author":"Lee","year":"2016","journal-title":"Journal of Gastroenterology and Hepatology"},{"key":"10.7717\/peerj.21196\/ref-58","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1158\/1078-0432.CCR-07-1615","article-title":"Identification of cystatin B as a potential serum marker in hepatocellular carcinoma","volume":"14","author":"Lee","year":"2008","journal-title":"Clinical Cancer Research"},{"key":"10.7717\/peerj.21196\/ref-59","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1021\/pr070525r","article-title":"Identification of hepatocellular-carcinoma-associated antigens and autoantibodies by serological proteome analysis combined with protein microarray","volume":"7","author":"Li","year":"2008","journal-title":"Journal of Proteome Research"},{"key":"10.7717\/peerj.21196\/ref-60","doi-asserted-by":"publisher","first-page":"9551","DOI":"10.18632\/oncotarget.3314","article-title":"Serum thioredoxin is a diagnostic marker for hepatocellular carcinoma","volume":"6","author":"Li","year":"2015","journal-title":"Oncotarget"},{"key":"10.7717\/peerj.21196\/ref-61","doi-asserted-by":"publisher","first-page":"8399","DOI":"10.1007\/s13277-015-3607-8","article-title":"Serum DLK1 is a potential prognostic biomarker in patients with hepatocellular carcinoma","volume":"36","author":"Li","year":"2015","journal-title":"Tumour Biology"},{"key":"10.7717\/peerj.21196\/ref-62","doi-asserted-by":"publisher","first-page":"10045","DOI":"10.18632\/oncotarget.3541","article-title":"Vasorin is a potential serum biomarker and drug target of hepatocarcinoma screened by subtractive-EMSA-SELEX to clinic patient serum","volume":"6","author":"Li","year":"2015","journal-title":"Oncotarget"},{"key":"10.7717\/peerj.21196\/ref-63","doi-asserted-by":"publisher","first-page":"e17494","DOI":"10.7717\/peerj.17494","article-title":"Anti-BIRC5 autoantibody serves as a valuable biomarker for diagnosing AFP-negative hepatocellular carcinoma","volume":"12","author":"Li","year":"2024","journal-title":"PeerJ"},{"key":"10.7717\/peerj.21196\/ref-64","doi-asserted-by":"publisher","first-page":"141","DOI":"10.5732\/cjc.012.10025","article-title":"Prognostic value of soluble MICA levels in the serum of patients with advanced hepatocellular carcinoma","volume":"32","author":"Li","year":"2013","journal-title":"Chinese Journal of Cancer"},{"key":"10.7717\/peerj.21196\/ref-65","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.cyto.2016.08.016","article-title":"CXCL13 rather than IL-31 is a potential indicator in patients with hepatocellular carcinoma","volume":"89","author":"Li","year":"2017","journal-title":"Cytokine"},{"key":"10.7717\/peerj.21196\/ref-66","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s12943-023-01844-5","article-title":"The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells","volume":"22","author":"Li","year":"2023","journal-title":"Molecular Cancer"},{"key":"10.7717\/peerj.21196\/ref-67","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12943-019-0948-8","article-title":"Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis","volume":"18","author":"Li","year":"2019","journal-title":"Molecular Cancer"},{"key":"10.7717\/peerj.21196\/ref-68","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/bjc.2012.494","article-title":"Identification of serum CCL15 in hepatocellular carcinoma","volume":"108","author":"Li","year":"2013","journal-title":"British Journal of Cancer"},{"key":"10.7717\/peerj.21196\/ref-69","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3233\/CBM-160533","article-title":"Clinical significance of serum 14-3-3 beta in patients with hepatocellular carcinoma","volume":"20","author":"Lin","year":"2017","journal-title":"Cancer Biomarkers"},{"key":"10.7717\/peerj.21196\/ref-70","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/s41392-021-00817-8","article-title":"Circulating tumor cells: biology and clinical significance","volume":"6","author":"Lin","year":"2021","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"10.7717\/peerj.21196\/ref-71","doi-asserted-by":"publisher","first-page":"e0127518","DOI":"10.1371\/journal.pone.0127518","article-title":"Association of serum level of growth differentiation factor 15 with liver cirrhosis and hepatocellular carcinoma","volume":"10","author":"Liu","year":"2015","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.21196\/ref-72","doi-asserted-by":"publisher","first-page":"38918","DOI":"10.1038\/srep38918","article-title":"Discovering potential serological biomarker for chronic Hepatitis B Virus-related hepatocellular carcinoma in Chinese population by MAL-associated serum glycoproteomics analysis","volume":"7","author":"Liu","year":"2017","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.21196\/ref-73","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jprot.2014.04.021","article-title":"The role of von Willebrand factor as a biomarker of tumor development in hepatitis B virus-associated human hepatocellular carcinoma: a quantitative proteomic based study","volume":"106","author":"Liu","year":"2014","journal-title":"Journal of Proteomics"},{"key":"10.7717\/peerj.21196\/ref-74","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.canep.2011.04.001","article-title":"Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system","volume":"36","author":"Liu","year":"2012","journal-title":"Cancer Epidemiology"},{"key":"10.7717\/peerj.21196\/ref-75","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nature Reviews Disease Primers"},{"key":"10.7717\/peerj.21196\/ref-76","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1177\/172460089601100307","article-title":"Serum CA125 as a marker of hepatocellular carcinoma","volume":"11","author":"Lopez","year":"1996","journal-title":"International Journal of Biological Markers"},{"key":"10.7717\/peerj.21196\/ref-77","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1002\/hep.31502","article-title":"Targeting tumor-associated antigens in hepatocellular carcinoma for immunotherapy: past pitfalls and future strategies","volume":"73","author":"Lu","year":"2021","journal-title":"Hepatology"},{"key":"10.7717\/peerj.21196\/ref-78","doi-asserted-by":"publisher","first-page":"1114594","DOI":"10.3389\/fmolb.2023.1114594","article-title":"Advances of multi-omics applications in hepatic precancerous lesions and hepatocellular carcinoma: the role of extracellular vesicles","volume":"10","author":"Lu","year":"2023","journal-title":"Frontiers in Molecular Biosciences"},{"key":"10.7717\/peerj.21196\/ref-79","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1245\/s10434-018-6402-0","article-title":"Application of serum annexin A3 in diagnosis, outcome prediction and therapeutic response evaluation for patients with hepatocellular carcinoma","volume":"25","author":"Ma","year":"2018","journal-title":"Annals of Surgical Oncology"},{"key":"10.7717\/peerj.21196\/ref-80","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1080\/08941939.2018.1535009","article-title":"Clinicopathological and prognostic value of plasma CD24 level in hepatocellular carcinoma","volume":"33","author":"Maimaitiming","year":"2020","journal-title":"Journal of Investigative Surgery"},{"key":"10.7717\/peerj.21196\/ref-81","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.22034\/APJCP.2018.19.6.1503","article-title":"Diagnostic and prognostic value of talin-1 and midkine as tumor markers in hepatocellular carcinoma in Egyptian patients","volume":"19","author":"Mashaly","year":"2018","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"10.7717\/peerj.21196\/ref-82","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1038\/nature17038","article-title":"Metastatic colonization by circulating tumour cells","volume":"529","author":"Massagu\u00e9","year":"2016","journal-title":"Nature"},{"key":"10.7717\/peerj.21196\/ref-83","doi-asserted-by":"publisher","first-page":"e103867","DOI":"10.1371\/journal.pone.0103867","article-title":"Serum autoantibody measurement for the detection of hepatocellular carcinoma","volume":"9","author":"Middleton","year":"2014","journal-title":"PLOS ONE"},{"key":"10.7717\/peerj.21196\/ref-84","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3390\/medicina57050503","article-title":"Foundational statistical principles in medical research: sensitivity, specificity, positive predictive value, and negative predictive value","volume":"57","author":"Monaghan","year":"2021","journal-title":"Medicina"},{"key":"10.7717\/peerj.21196\/ref-85","doi-asserted-by":"publisher","first-page":"5826","DOI":"10.3748\/wjg.v20.i19.5826","article-title":"Identification of biomarkers for hepatocellular carcinoma by semiquantitative immunocytochemistry","volume":"20","author":"Mu","year":"2014","journal-title":"World Journal of Gastroenterology"},{"key":"10.7717\/peerj.21196\/ref-86","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1002\/ijc.28020","article-title":"Human liver carboxylesterase 1 outperforms alpha-fetoprotein as biomarker to discriminate hepatocellular carcinoma from other liver diseases in Korean patients","volume":"133","author":"Na","year":"2013","journal-title":"International Journal of Cancer"},{"key":"10.7717\/peerj.21196\/ref-87","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.clinbiochem.2012.04.024","article-title":"Clinical significance of serum clusterin as a biomarker for evaluating diagnosis and metastasis potential of viral-related hepatocellular carcinoma","volume":"45","author":"Nafee","year":"2012","journal-title":"Clinical Biochemistry"},{"key":"10.7717\/peerj.21196\/ref-88","doi-asserted-by":"publisher","first-page":"1257","DOI":"10.1016\/j.clinbiochem.2014.05.002","article-title":"Inter-alpha-trypsin inhibitor heavy chain H4 as a diagnostic and prognostic indicator in patients with hepatitis B virus-associated hepatocellular carcinoma","volume":"47","author":"Noh","year":"2014","journal-title":"Clinical Biochemistry"},{"key":"10.7717\/peerj.21196\/ref-89","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1002\/ijc.33165","article-title":"Six autoantibodies as potential serum biomarkers of hepatocellular carcinoma: a prospective multicenter study","volume":"147","author":"Okada","year":"2020","journal-title":"International Journal of Cancer"},{"key":"10.7717\/peerj.21196\/ref-90","doi-asserted-by":"publisher","first-page":"7825","DOI":"10.7314\/apjcp.2015.16.17.7825","article-title":"Serum beta-2 microglobulin: a possible marker for disease progression in Egyptian patients with chronic HCV related liver diseases","volume":"16","author":"Ouda","year":"2015","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"10.7717\/peerj.21196\/ref-91","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/0959-8049(95)00542-0","article-title":"Prognostic value of serum alpha-1-antitrypsin in hepatocellular carcinoma","volume":"32A","author":"Pirisi","year":"1996","journal-title":"European Journal of Cancer"},{"key":"10.7717\/peerj.21196\/ref-92","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1111\/jgh.12576","article-title":"Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC)","volume":"29","author":"Pozzan","year":"2014","journal-title":"Journal of Gastroenterology and Hepatology"},{"key":"10.7717\/peerj.21196\/ref-93","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1002\/pmic.201300226","article-title":"Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma","volume":"14","author":"Qi","year":"2014","journal-title":"Proteomics"},{"key":"10.7717\/peerj.21196\/ref-94","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1089\/gtmb.2017.0230","article-title":"The role of dermcidin in the diagnosis and staging of hepatocellular carcinoma","volume":"22","author":"Qiu","year":"2018","journal-title":"Genetic Testing and Molecular Biomarkers"},{"key":"10.7717\/peerj.21196\/ref-95","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1111\/j.1440-1746.2010.06491.x","article-title":"Ubiquitin-proteasome profiling for enhanced detection of hepatocellular carcinoma in patients with chronic liver disease","volume":"26","author":"Qu","year":"2011","journal-title":"Journal of Gastroenterology and Hepatology"},{"key":"10.7717\/peerj.21196\/ref-96","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1097\/ALN.0b013e3181d47604","article-title":"Statistical evaluation of a biomarker","volume":"112","author":"Ray","year":"2010","journal-title":"Anesthesiology"},{"key":"10.7717\/peerj.21196\/ref-97","first-page":"5996","article-title":"Interleukin-8 serum levels in patients with hepatocellular carcinoma: correlations with clinicopathological features and prognosis","volume":"9","author":"Ren","year":"2003","journal-title":"Clinical Cancer Research"},{"key":"10.7717\/peerj.21196\/ref-98","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3390\/vaccines8030371","article-title":"The landscape of tumor-specific antigens in colorectal cancer","volume":"8","author":"Rus\u00a0Bakarurraini","year":"2020","journal-title":"Vaccine"},{"key":"10.7717\/peerj.21196\/ref-99","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.3390\/biom12081021","article-title":"Molecular biomarkers in cancer","volume":"12","author":"Sarhadi","year":"2022","journal-title":"Biomolecules"},{"key":"10.7717\/peerj.21196\/ref-100","doi-asserted-by":"publisher","first-page":"10644","DOI":"10.3390\/ijms241310644","article-title":"Liquid biopsy in hepatocellular carcinoma: the significance of circulating tumor cells in diagnosis, prognosis, and treatment monitoring","volume":"24","author":"Shaik","year":"2023","journal-title":"International Journal of Molecular Sciences"},{"key":"10.7717\/peerj.21196\/ref-101","doi-asserted-by":"publisher","first-page":"543","DOI":"10.3892\/ijo.2015.3042","article-title":"C-reactive protein is a biomarker of AFP-negative HBV-related hepatocellular carcinoma","volume":"47","author":"She","year":"2015","journal-title":"International Journal of Oncology"},{"key":"10.7717\/peerj.21196\/ref-102","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1158\/1940-6207.CAPR-23-0311","article-title":"Combination of an autoantibody panel and alpha-fetoprotein for early detection of hepatitis B virus-associated hepatocellular carcinoma","volume":"17","author":"Shen","year":"2024","journal-title":"Cancer Prevention Research"},{"key":"10.7717\/peerj.21196\/ref-103","doi-asserted-by":"publisher","first-page":"101695","DOI":"10.1016\/j.bbrep.2024.101695","article-title":"Advances and challenges of exosome-derived noncoding RNAs for hepatocellular carcinoma diagnosis and treatment","volume":"38","author":"Shi","year":"2024","journal-title":"Biochemistry and Biophysics Reports"},{"key":"10.7717\/peerj.21196\/ref-104","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.7314\/apjcp.2014.15.7.2979","article-title":"Serum peroxiredoxin3 is a useful biomarker for early diagnosis and assessemnt of prognosis of hepatocellular carcinoma in Chinese patients","volume":"15","author":"Shi","year":"2014","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"10.7717\/peerj.21196\/ref-105","doi-asserted-by":"publisher","first-page":"15788","DOI":"10.1038\/s41598-019-52356-6","article-title":"Serum milk fat globule-EGF factor 8 (MFG-E8) as a diagnostic and prognostic biomarker in patients with hepatocellular carcinoma","volume":"9","author":"Shimagaki","year":"2019","journal-title":"Scientific Reports"},{"key":"10.7717\/peerj.21196\/ref-106","doi-asserted-by":"publisher","first-page":"3890","DOI":"10.1158\/1078-0432.CCR-22-0569","article-title":"Extracellular vesicles may predict response to radioembolization and sorafenib treatment in advanced hepatocellular carcinoma: an exploratory analysis from the SORAMIC trial","volume":"28","author":"Shuen","year":"2022","journal-title":"Clinical Cancer Research"},{"key":"10.7717\/peerj.21196\/ref-107","doi-asserted-by":"publisher","first-page":"e125\u2013131","DOI":"10.5301\/JBM.2012.9097","article-title":"The role of chemokine CC ligand 20 in patients with liver cirrhosis and hepatocellular carcinoma","volume":"27","author":"Soliman","year":"2012","journal-title":"International Journal of Biological Markers"},{"key":"10.7717\/peerj.21196\/ref-108","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/cncr.10170","article-title":"Transforming growth factor-beta1 as a useful serologic marker of small hepatocellular carcinoma","volume":"94","author":"Song","year":"2002","journal-title":"Cancer"},{"key":"10.7717\/peerj.21196\/ref-109","doi-asserted-by":"publisher","first-page":"789","DOI":"10.4143\/crt.2019.749","article-title":"Soluble Axl is a novel diagnostic biomarker of hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection","volume":"52","author":"Song","year":"2020","journal-title":"Cancer Research and Treatment"},{"key":"10.7717\/peerj.21196\/ref-110","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jcp.2008.061010","article-title":"Receiver-operating characteristic curve analysis in diagnostic, prognostic and predictive biomarker research","volume":"62","author":"S\u00f8reide","year":"2009","journal-title":"Journal of Clinical Pathology"},{"key":"10.7717\/peerj.21196\/ref-111","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1093\/carcin\/bgs372","article-title":"Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma","volume":"34","author":"Sun","year":"2013","journal-title":"Carcinogenesis"},{"key":"10.7717\/peerj.21196\/ref-112","doi-asserted-by":"publisher","first-page":"342518","DOI":"10.1016\/j.aca.2024.342518","article-title":"Low-abundance proteins-based label-free SERS approach for high precision detection of liver cancer with different stages","volume":"1304","author":"Sun","year":"2024","journal-title":"Analytica Chimica Acta"},{"key":"10.7717\/peerj.21196\/ref-113","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1021\/pr901085z","article-title":"Proteomics of hepatocellular carcinoma: serum vimentin as a surrogate marker for small tumors (