{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T23:37:50Z","timestamp":1772667470047,"version":"3.50.1"},"reference-count":156,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T00:00:00Z","timestamp":1589932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["410853455"],"award-info":[{"award-number":["410853455"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the third most common cause of cancer-related death. One of the major problems faced by researchers and clinicians in this area is the lack of reliable disease biomarkers, which would allow for an earlier diagnosis, follow-up or prediction of treatment response, among others. In this regard, the \u201cHCC circulome\u201d, defined as the pool of circulating molecules in the bloodstream derived from the primary tumor, represents an appealing target, the so called liquid biopsy. Such molecules encompass circulating tumor proteins, circulating tumor cells (CTCs), extracellular vesicles (EVs), tumor-educated platelets (TEPs), and circulating tumor nucleic acids, namely circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA). In this article, we summarize recent findings highlighting the promising role of liquid biopsies as novel potential biomarkers in HCC, emphasizing on its clinical performance.<\/jats:p>","DOI":"10.3390\/jcm9051541","type":"journal-article","created":{"date-parts":[[2020,5,20]],"date-time":"2020-05-20T10:37:38Z","timestamp":1589971058000},"page":"1541","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Liquid Biopsies in Hepatocellular Carcinoma: Are We Winning?"],"prefix":"10.3390","volume":"9","author":[{"given":"Tudor","family":"Mocan","sequence":"first","affiliation":[{"name":"Octavian Fodor Institute for Gastroenterology and Hepatology, Iuliu Ha\u0163ieganu, University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-1089","authenticated-orcid":false,"given":"Andr\u00e9 L.","family":"Sim\u00e3o","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-0091","authenticated-orcid":false,"given":"Rui E.","family":"Castro","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4829-754X","authenticated-orcid":false,"given":"Cec\u00edlia M. P.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4137-2981","authenticated-orcid":false,"given":"Artur","family":"S\u0142omka","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Nicolaus Copernicus University in Toru\u0144, Ludwik Rydygier Collegium Medicum, 85-094 Bydgoszcz, Poland"}]},{"given":"Bingduo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany"}]},{"given":"Christian","family":"Strassburg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany"}]},{"given":"Aliona","family":"W\u00f6hler","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital Koblenz, 56072 Koblenz, Germany"}]},{"given":"Arnulf G.","family":"Willms","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital Koblenz, 56072 Koblenz, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1682-1765","authenticated-orcid":false,"given":"Miroslaw","family":"Kornek","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(18)30010-2","article-title":"Hepatocellular carcinoma","volume":"391","author":"Forner","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1001\/jamaoncol.2017.3055","article-title":"The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015","volume":"3","author":"Akinyemiju","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.jhep.2014.03.037","article-title":"Estimation of lead-time bias and its impact on the outcome of surveillance for the early diagnosis of hepatocellular carcinoma","volume":"61","author":"Cucchetti","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"iii1","DOI":"10.1136\/gut.52.suppl_3.iii1","article-title":"Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults","volume":"52","author":"Ryder","year":"2003","journal-title":"Gut"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3322\/canjclin.25.4.204","article-title":"CEA, AFP and other potential tumor markers","volume":"25","author":"Zamcheck","year":"1975","journal-title":"CA Cancer J. Clin."},{"key":"ref_6","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","year":"2014","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"452","DOI":"10.4254\/wjh.v10.i7.452","article-title":"Contemporary role of liver biopsy in hepatocellular carcinoma","volume":"10","author":"Sparchez","year":"2018","journal-title":"World J. Hepatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1158\/1078-0432.CCR-14-1429","article-title":"Translational implications of tumor heterogeneity","volume":"21","author":"Quezada","year":"2015","journal-title":"Clin. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ccell.2014.12.001","article-title":"Biological and therapeutic impact of intratumor heterogeneity in cancer evolution","volume":"27","author":"McGranahan","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1002\/hep.26526","article-title":"Sublethal heat treatment promotes epithelial-mesenchymal transition and enhances the malignant potential of hepatocellular carcinoma","volume":"58","author":"Yoshida","year":"2013","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s12029-016-9801-0","article-title":"Liquid Biopsy and its Potential for Management of Hepatocellular Carcinoma","volume":"47","author":"Zhou","year":"2016","journal-title":"J. Gastrointest. Cancer"},{"key":"ref_13","first-page":"263","article-title":"Liquid biopsy in liver cancer","volume":"19","author":"Labgaa","year":"2015","journal-title":"Discov. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13046-018-0893-1","article-title":"Clinical applications of liquid biopsy as prognostic and predictive biomarkers in hepatocellular carcinoma: Circulating tumor cells and circulating tumor DNA","volume":"37","author":"Li","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1427849","DOI":"10.1155\/2016\/1427849","article-title":"Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers","volume":"2016","author":"Yin","year":"2016","journal-title":"Dis. Markers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"100","DOI":"10.2298\/SARH1502100N","article-title":"Fifty years of discovery of alpha-fetoprotein as the first tumor marker","volume":"143","author":"Nikulina","year":"2015","journal-title":"Srp. Arh. Celok. Lek."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0009-8981(01)00644-1","article-title":"AFP-L3: A new generation of tumor marker for hepatocellular carcinoma","volume":"313","author":"Li","year":"2001","journal-title":"Clin. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1053\/j.gastro.2009.04.005","article-title":"Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma","volume":"137","author":"Marrero","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.3748\/wjg.v12.i8.1175","article-title":"Serum tumor markers for detection of hepatocellular carcinoma","volume":"12","author":"Zhou","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_20","first-page":"47","article-title":"Hepatocellular carcinoma\u2014From immunobiology to immunotherapy","volume":"50","author":"Flecken","year":"2012","journal-title":"Z. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cgh.2013.10.038","article-title":"Update on biomarkers of hepatocellular carcinoma","volume":"13","author":"Chaiteerakij","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1053\/jhep.2003.50195","article-title":"Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients","volume":"37","author":"Marrero","year":"2003","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1111\/liv.14223","article-title":"Biology and significance of alpha-fetoprotein in hepatocellular carcinoma","volume":"39","author":"Galle","year":"2019","journal-title":"Liver Int."},{"key":"ref_24","unstructured":"European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol., 69, 182\u2013236."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1111\/j.1572-0241.2006.00681.x","article-title":"Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size","volume":"101","author":"Nakamura","year":"2006","journal-title":"Am. J. Gastroenterol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S1542-3565(05)00855-4","article-title":"Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma","volume":"4","author":"Toyoda","year":"2006","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1097\/PAP.0b013e3181992455","article-title":"Glypican-3: A novel diagnostic marker for hepatocellular carcinoma and more","volume":"16","author":"Kandil","year":"2009","journal-title":"Adv. Anat. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/med.21455","article-title":"Glypican-3: A promising biomarker for hepatocellular carcinoma diagnosis and treatment","volume":"38","author":"Zhou","year":"2018","journal-title":"Med. Res. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37835","DOI":"10.18632\/oncotarget.14271","article-title":"Perioperative plasma glypican-3 level may enable prediction of the risk of recurrence after surgery in patients with stage I hepatocellular carcinoma","volume":"8","author":"Ofuji","year":"2017","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fonc.2019.00248","article-title":"Next-Generation Cancer Immunotherapy Targeting Glypican-3","volume":"9","author":"Shimizu","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0016-5085(03)00689-9","article-title":"Glypican-3: A novel serum and histochemical marker for hepatocellular carcinoma","volume":"125","author":"Capurro","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/PAP.0000000000000043","article-title":"Discovery and diagnostic value of a novel oncofetal protein: Glypican 3","volume":"21","author":"Wang","year":"2014","journal-title":"Adv. Anat. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2165\/00063030-200519020-00001","article-title":"Usefulness of the novel oncofetal antigen glypican-3 for diagnosis of hepatocellular carcinoma and melanoma","volume":"19","author":"Nakatsura","year":"2005","journal-title":"BioDrugs"},{"key":"ref_34","first-page":"1013","article-title":"Serum VEGF as a tumor marker in patients with HCV-related liver cirrhosis and hepatocellular carcinoma","volume":"33","author":"Mukozu","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1177\/107327480501200407","article-title":"Enhanced detection of hepatocellular carcinoma","volume":"12","author":"Mohammed","year":"2005","journal-title":"Cancer Control"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1038\/sj.bjc.6603923","article-title":"Where is VEGF in the body? A meta-analysis of VEGF distribution in cancer","volume":"97","author":"Kut","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1158\/1078-0432.CCR-11-2175","article-title":"Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma","volume":"18","author":"Llovet","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9137","DOI":"10.1038\/s41598-019-45537-w","article-title":"Circulating pro- and anti-angiogenic factors in multi-stage liver disease and hepatocellular carcinoma progression","volume":"9","author":"Joo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/hep.24703","article-title":"Identification of osteopontin as a novel marker for early hepatocellular carcinoma","volume":"55","author":"Shang","year":"2012","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s11901-017-0349-7","article-title":"Should AFP (or any biomarkers) be used for HCC surveillance?","volume":"16","author":"Roberts","year":"2017","journal-title":"Curr. Hepatol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nature11708","article-title":"Metabolic phenotyping in clinical and surgical environments","volume":"491","author":"Nicholson","year":"2012","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1002\/hep.26130","article-title":"Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma","volume":"57","author":"Wang","year":"2013","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fages, A., Duarte-Salles, T., Stepien, M., Ferrari, P., Fedirko, V., Pontoizeau, C., Trichopoulou, A., Aleksandrova, K., Tjonneland, A., and Olsen, A. (2015). Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort. BMC Med., 13.","DOI":"10.1186\/s12916-015-0462-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.aca.2009.06.033","article-title":"Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography\/mass spectrometry","volume":"648","author":"Wu","year":"2009","journal-title":"Anal. Chim. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.1158\/0008-5472.CAN-13-0308","article-title":"Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics","volume":"73","author":"Huang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1021\/pr500390y","article-title":"Metabolomics study of hepatocellular carcinoma: Discovery and validation of serum potential biomarkers by using capillary electrophoresis-mass spectrometry","volume":"13","author":"Zeng","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/ijc.28706","article-title":"NMR and LC\/MS-based global metabolomics to identify serum biomarkers differentiating hepatocellular carcinoma from liver cirrhosis","volume":"135","author":"Liu","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/bjc.2015.38","article-title":"Proteomic and metabonomic biomarkers for hepatocellular carcinoma: A comprehensive review","volume":"112","author":"Kimhofer","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1007\/s00216-011-5245-3","article-title":"Identification of serum biomarkers of hepatocarcinoma through liquid chromatography\/mass spectrometry-based metabonomic method","volume":"401","author":"Chen","year":"2011","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5433","DOI":"10.1021\/pr300683a","article-title":"Serum metabolic profiling study of hepatocellular carcinoma infected with hepatitis B or hepatitis C virus by using liquid chromatography-mass spectrometry","volume":"11","author":"Zhou","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1021\/pr500973d","article-title":"Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery","volume":"14","author":"Shao","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1158\/0008-5472.CAN-15-3199","article-title":"Acetylcarnitine Is a Candidate Diagnostic and Prognostic Biomarker of Hepatocellular Carcinoma","volume":"76","author":"Lu","year":"2016","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1002\/hep.29789","article-title":"cHCC-CCA: Consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation","volume":"68","author":"Brunt","year":"2018","journal-title":"Hepatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"16294","DOI":"10.1038\/srep16294","article-title":"Comprehensive analysis of transcriptome and metabolome analysis in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma","volume":"5","author":"Murakami","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2147\/HMER.S193996","article-title":"Characterization of the urinary metabolic profile of cholangiocarcinoma in a United Kingdom population","volume":"11","author":"Alsaleh","year":"2019","journal-title":"Hepat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/hep.30319","article-title":"Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis","volume":"70","author":"Banales","year":"2018","journal-title":"Hepatology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1126\/science.1235226","article-title":"Circulating tumor cells","volume":"341","author":"Plaks","year":"2013","journal-title":"Science"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1159\/000430382","article-title":"Circulating Tumor Cells for Predicting the Prognostic of Patients with Hepatocellular Carcinoma: A Meta Analysis","volume":"37","author":"Fan","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e7513","DOI":"10.1097\/MD.0000000000007513","article-title":"The diagnostic value of assays for circulating tumor cells in hepatocellular carcinoma: A meta-analysis","volume":"96","author":"Sun","year":"2017","journal-title":"Medicine"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/s12072-016-9732-7","article-title":"An improved strategy to detect the epithelial-mesenchymal transition process in circulating tumor cells in hepatocellular carcinoma patients","volume":"10","author":"Liu","year":"2016","journal-title":"Hepatol. Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.7150\/thno.15284","article-title":"Aptamer-Mediated Transparent-Biocompatible Nanostructured Surfaces for Hepotocellular Circulating Tumor Cells Enrichment","volume":"6","author":"Wang","year":"2016","journal-title":"Theranostics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1073\/pnas.1617032114","article-title":"An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma","volume":"114","author":"Kalinich","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.canlet.2016.04.033","article-title":"AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis","volume":"378","author":"Jin","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11570","DOI":"10.1038\/s41598-018-30047-y","article-title":"High-density single cell mRNA sequencing to characterize circulating tumor cells in hepatocellular carcinoma","volume":"8","author":"Craig","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1002\/lt.25062","article-title":"A novel multimarker assay for the phenotypic profiling of circulating tumor cells in hepatocellular carcinoma","volume":"24","author":"Court","year":"2018","journal-title":"Liver Transpl."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.humpath.2003.08.026","article-title":"Frequent EpCam protein expression in human carcinomas","volume":"35","author":"Went","year":"2004","journal-title":"Hum. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.jvir.2018.07.030","article-title":"High Epithelial Cell Adhesion Molecule-Positive Circulating Tumor Cell Count Predicts Poor Survival of Patients with Unresectable Hepatocellular Carcinoma Treated with Transcatheter Arterial Chemoembolization","volume":"29","author":"Shen","year":"2018","journal-title":"J. Vasc. Interv. Radiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"89978","DOI":"10.18632\/oncotarget.21208","article-title":"Circulating tumor cells as liquid biomarker for high HCC recurrence risk after curative liver resection","volume":"8","author":"Schulze","year":"2017","journal-title":"Oncotarget"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Wang, B., Wu, J., Zhang, C., Zhou, Y., Yang, X., Zhou, J., Guo, W., and Fan, J. (2016). Association of preoperative EpCAM Circulating Tumor Cells and peripheral Treg cell levels with early recurrence of hepatocellular carcinoma following radical hepatic resection. BMC Cancer, 16.","DOI":"10.1186\/s12885-016-2526-4"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1126\/science.1253533","article-title":"Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility","volume":"345","author":"Yu","year":"2014","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nprot.2017.125","article-title":"Expansion of patient-derived circulating tumor cells from liquid biopsies using a CTC microfluidic culture device","volume":"13","author":"Khoo","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1365-2141.1967.tb08741.x","article-title":"The nature and significance of platelet products in human plasma","volume":"13","author":"Wolf","year":"1967","journal-title":"Br. J. Haematol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.3389\/fimmu.2018.02723","article-title":"Large Extracellular Vesicles: Have We Found the Holy Grail of Inflammation?","volume":"9","author":"Slomka","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41556-018-0250-9","article-title":"Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication","volume":"21","author":"Mathieu","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/ncb1596","article-title":"Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells","volume":"9","author":"Valadi","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/nri855","article-title":"Exosomes: Composition, biogenesis and function","volume":"2","author":"Thery","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/978-3-319-67577-0_6","article-title":"Exosomes in Cancer: Another Mechanism of Tumor-Induced Immune Suppression","volume":"1036","author":"Whiteside","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"26913","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles","volume":"3","author":"Lotvall","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Thery","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/hep4.1300","article-title":"Extracellular Vesicles in Liver Diseases: Meeting Report from the International Liver Congress 2018","volume":"3","author":"Banales","year":"2019","journal-title":"Hepatol. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1055\/s-0038-1676122","article-title":"Extracellular Vesicles in Liver Diseases: Diagnostic, Prognostic, and Therapeutic Application","volume":"39","author":"Urban","year":"2019","journal-title":"Semin. Liver Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-cellbio-101512-122326","article-title":"Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles","volume":"30","author":"Colombo","year":"2014","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Abbate, V., Marcantoni, M., Giuliante, F., Vecchio, F.M., Gatto, I., Mele, C., Saviano, A., Arciuolo, D., Gaetani, E., and Ferrari, M.C. (2017). HepPar1-Positive Circulating Microparticles Are Increased in Subjects with Hepatocellular Carcinoma and Predict Early Recurrence after Liver Resection. Int. J. Mol. Sci., 18.","DOI":"10.20944\/preprints201704.0181.v1"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jhep.2017.02.024","article-title":"Cancer-associated circulating large extracellular vesicles in cholangiocarcinoma and hepatocellular carcinoma","volume":"67","author":"Urban","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_85","doi-asserted-by":"crossref","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":"ref_86","doi-asserted-by":"crossref","first-page":"930","DOI":"10.3389\/fphys.2018.00930","article-title":"Extracellular Vesicle-Associated mir-21 and mir-144 Are Markedly Elevated in Serum of Patients with Hepatocellular Carcinoma","volume":"9","author":"Pu","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1007\/s00432-015-1943-0","article-title":"Combination of exosomes and circulating microRNAs may serve as a promising tumor marker complementary to alpha-fetoprotein for early-stage hepatocellular carcinoma diagnosis in rats","volume":"141","author":"Liu","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1002\/cam4.1390","article-title":"Serum exosomal microRNAs combined with alpha-fetoprotein as diagnostic markers of hepatocellular carcinoma","volume":"7","author":"Wang","year":"2018","journal-title":"Cancer Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.tips.2019.01.006","article-title":"Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis","volume":"40","author":"Bebawy","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"46","DOI":"10.21037\/atm.2017.01.32","article-title":"The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer?","volume":"5","author":"Kwapisz","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ctrv.2016.02.008","article-title":"Personalized therapy for hepatocellular carcinoma: Where are we now?","volume":"45","author":"Chan","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"ref_92","first-page":"241","article-title":"Les acides nucleiques du plasma sanguin chez l\u2019homme","volume":"142","author":"Mandel","year":"1948","journal-title":"C. R. Seances Soc. Biol. Fil."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.phrs.2018.08.017","article-title":"Circulating tumor DNA\u2013Current state of play and future perspectives","volume":"136","author":"Krishnan","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_94","first-page":"4713","article-title":"Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma","volume":"26","author":"Iizuka","year":"2006","journal-title":"Anticancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ijid.2017.12.002","article-title":"Diagnostic value of circulating cell-free DNA levels for hepatocellular carcinoma","volume":"67","author":"Yan","year":"2018","journal-title":"Int. J. Infect. Dis."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5745","DOI":"10.2147\/CMAR.S197455","article-title":"Detection of a novel panel of somatic mutations in plasma cell-free DNA and its diagnostic value in hepatocellular carcinoma","volume":"11","author":"Xiong","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1002\/hep.29913","article-title":"Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases","volume":"68","author":"Marrero","year":"2018","journal-title":"Hepatology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"E1317","DOI":"10.1073\/pnas.1500076112","article-title":"Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients","volume":"112","author":"Jiang","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.7150\/jca.15618","article-title":"Plasma Circulating Cell-free DNA Integrity as a Promising Biomarker for Diagnosis and Surveillance in Patients with Hepatocellular Carcinoma","volume":"7","author":"Huang","year":"2016","journal-title":"J. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"E10925","DOI":"10.1073\/pnas.1814616115","article-title":"Preferred end coordinates and somatic variants as signatures of circulating tumor DNA associated with hepatocellular carcinoma","volume":"115","author":"Jiang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","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","year":"2015","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1038\/s41388-018-0206-3","article-title":"A pilot study of ultra-deep targeted sequencing of plasma DNA identifies driver mutations in hepatocellular carcinoma","volume":"37","author":"Labgaa","year":"2018","journal-title":"Oncogene"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejca.2019.04.014","article-title":"Identification of mutations in circulating cell-free tumour DNA as a biomarker in hepatocellular carcinoma","volume":"116","author":"Howell","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/annonc\/mdy083","article-title":"Genetic profiling using plasma-derived cell-free DNA in therapy-naive hepatocellular carcinoma patients: A pilot study","volume":"29","author":"Ng","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"40481","DOI":"10.18632\/oncotarget.9629","article-title":"Noninvasive detection of tumor-associated mutations from circulating cell-free DNA in hepatocellular carcinoma patients by targeted deep sequencing","volume":"7","author":"Liao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1186\/s12967-019-2079-9","article-title":"Circulating DNA as prognostic biomarker in patients with advanced hepatocellular carcinoma: A translational exploratory study from the SORAMIC trial","volume":"17","author":"Ronsch","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jhep.2017.03.005","article-title":"Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma","volume":"67","author":"Huang","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.trsl.2018.07.001","article-title":"Liquid biopsies for hepatocellular carcinoma","volume":"201","author":"Su","year":"2018","journal-title":"Transl. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6107","DOI":"10.1158\/1078-0432.CCR-18-3341","article-title":"Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA","volume":"25","author":"Kaseb","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_110","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","year":"2016","journal-title":"J. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1126\/science.aar3247","article-title":"Detection and localization of surgically resectable cancers with a multi-analyte blood test","volume":"359","author":"Cohen","year":"2018","journal-title":"Science"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6308","DOI":"10.1073\/pnas.1819799116","article-title":"Detection of early-stage hepatocellular carcinoma in asymptomatic HBsAg-seropositive individuals by liquid biopsy","volume":"116","author":"Qu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/hep4.1187","article-title":"Telomerase reverse transcriptase mutations in plasma DNA in patients with hepatocellular carcinoma or cirrhosis: Prevalence and risk factors","volume":"2","author":"Jiao","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"78","DOI":"10.3389\/fmed.2018.00078","article-title":"Circulating Cell-Free DNA in Hepatocellular Carcinoma: Current Insights and Outlook","volume":"5","author":"Ng","year":"2018","journal-title":"Front. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nmat4997","article-title":"Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma","volume":"16","author":"Xu","year":"2017","journal-title":"Nat. Mater."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10238-017-0473-2","article-title":"Detection of promoter methylation status of suppressor of cytokine signaling 3 (SOCS3) in tissue and plasma from Chinese patients with different hepatic diseases","volume":"18","author":"Wei","year":"2018","journal-title":"Clin. Exp. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2929381","DOI":"10.1155\/2017\/2929381","article-title":"Diagnostic Value of the Methylation of Multiple Gene Promoters in Serum in Hepatitis B Virus-Related Hepatocellular Carcinoma","volume":"2017","author":"Dong","year":"2017","journal-title":"Dis. Markers"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"6406","DOI":"10.18632\/oncotarget.14115","article-title":"Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma","volume":"8","author":"Lu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1136\/gutjnl-2019-318882","article-title":"Genome-wide mapping of 5-hydroxymethylcytosines in circulating cell-free DNA as a non-invasive approach for early detection of hepatocellular carcinoma","volume":"68","author":"Cai","year":"2019","journal-title":"Gut"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"795","DOI":"10.4149\/neo_2017_519","article-title":"Combination of LINE-1 hypomethylation and RASSF1A promoter hypermethylation in serum DNA is a non-invasion prognostic biomarker for early recurrence of hepatocellular carcinoma after curative resection","volume":"64","author":"Liu","year":"2017","journal-title":"Neoplasma"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Holmila, R., Sklias, A., Muller, D.C., Degli Esposti, D., Guilloreau, P., McKay, J., Sangrajrang, S., Srivatanakul, P., Hainaut, P., and Merle, P. (2017). Targeted deep sequencing of plasma circulating cell-free DNA reveals Vimentin and Fibulin 1 as potential epigenetic biomarkers for hepatocellular carcinoma. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0174265"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ebiom.2018.03.029","article-title":"Plasma mSEPT9: A Novel Circulating Cell-free DNA-Based Epigenetic Biomarker to Diagnose Hepatocellular Carcinoma","volume":"30","author":"Oussalah","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"7239","DOI":"10.7150\/thno.35573","article-title":"Genome-wide discovery and validation of diagnostic DNA methylation-based biomarkers for hepatocellular cancer detection in circulating cell free DNA","volume":"9","author":"Hlady","year":"2019","journal-title":"Theranostics"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e1549","DOI":"10.1038\/cddis.2014.518","article-title":"A novel biomarker Linc00974 interacting with KRT19 promotes proliferation and metastasis in hepatocellular carcinoma","volume":"5","author":"Tang","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s40291-016-0200-9","article-title":"Evaluation of Circulatory RNA-Based Biomarker Panel in Hepatocellular Carcinoma","volume":"20","author":"Matboli","year":"2016","journal-title":"Mol. Diagn. Ther."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1159\/000484589","article-title":"Circulating LncRNAs Serve as Diagnostic Markers for Hepatocellular Carcinoma","volume":"44","author":"Yuan","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Pezzuto, F., Buonaguro, L., Buonaguro, F.M., and Tornesello, M.L. (2018). The Role of Circulating Free DNA and MicroRNA in Non-Invasive Diagnosis of HBV- and HCV-Related Hepatocellular Carcinoma. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041007"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3713","DOI":"10.3748\/wjg.v23.i20.3713","article-title":"Study on the value of serum miR-106b for the early diagnosis of hepatocellular carcinoma","volume":"23","author":"Shi","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"5650","DOI":"10.3748\/wjg.v23.i31.5650","article-title":"Liquid biopsy in patients with hepatocellular carcinoma: Circulating tumor cells and cell-free nucleic acids","volume":"23","author":"Okajima","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nrgastro.2013.87","article-title":"MicroRNAs in liver disease","volume":"10","author":"Szabo","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Povero, D., Eguchi, A., Li, H., Johnson, C.D., Papouchado, B.G., Wree, A., Messer, K., and Feldstein, A.E. (2014). Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0113651"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1136\/gutjnl-2014-306996","article-title":"Circulating microRNA signature in non-alcoholic fatty liver disease: From serum non-coding RNAs to liver histology and disease pathogenesis","volume":"64","author":"Pirola","year":"2015","journal-title":"Gut"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1002\/hep.25873","article-title":"Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases","volume":"56","author":"Bala","year":"2012","journal-title":"Hepatology"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"66402","DOI":"10.18632\/oncotarget.18949","article-title":"Circulating miRNAs as novel diagnostic biomarkers in hepatocellular carcinoma detection: A meta-analysis based on 24 articles","volume":"8","author":"Ding","year":"2017","journal-title":"Oncotarget"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3892\/ijo.2013.1965","article-title":"MicroRNA-21 regulates the migration and invasion of a stem-like population in hepatocellular carcinoma","volume":"43","author":"Zhou","year":"2013","journal-title":"Int. J. Oncol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.gene.2015.08.038","article-title":"The potential role of miRNAs 21 and 199-a in early diagnosis of hepatocellular carcinoma","volume":"575","author":"Amr","year":"2016","journal-title":"Gene"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/j.clinre.2015.11.002","article-title":"Serum miR-21, miR-26a and miR-101 as potential biomarkers of hepatocellular carcinoma","volume":"40","author":"Zhuang","year":"2016","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/carcin\/bgx026","article-title":"Small non-coding RNA and cancer","volume":"38","author":"Romano","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"12273","DOI":"10.1007\/s13277-016-5097-8","article-title":"Serum microRNA panels as potential biomarkers for early detection of hepatocellular carcinoma on top of HCV infection","volume":"37","author":"Zekri","year":"2016","journal-title":"Tumour Biol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.3748\/wjg.v24.i24.2596","article-title":"Novel serum microRNAs panel on the diagnostic and prognostic implications of hepatocellular carcinoma","volume":"24","author":"An","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"15350","DOI":"10.18632\/oncotarget.24601","article-title":"Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma","volume":"9","author":"Moshiri","year":"2018","journal-title":"Oncotarget"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Weis, A., Marquart, L., Calvopina, D.A., Genz, B., Ramm, G.A., and Skoien, R. (2019). Serum MicroRNAs as Biomarkers in Hepatitis C: Preliminary Evidence of a MicroRNA Panel for the Diagnosis of Hepatocellular Carcinoma. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040864"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/hep4.1451","article-title":"Highly Sensitive Circulating MicroRNA Panel for Accurate Detection of Hepatocellular Carcinoma in Patients With Liver Disease","volume":"4","author":"Yamamoto","year":"2020","journal-title":"Hepatol. Commun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e5642","DOI":"10.1097\/MD.0000000000005642","article-title":"Serum microRNA panel for early diagnosis of the onset of hepatocellular carcinoma","volume":"96","author":"Zhang","year":"2017","journal-title":"Medicine"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.dld.2018.12.011","article-title":"Meta-analysis of circulating microRNAs for the diagnosis of hepatocellular carcinoma","volume":"51","author":"Peng","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"53820","DOI":"10.18632\/oncotarget.10781","article-title":"Circulating microRNA profiles in plasma: Identification of miR-224 as a novel diagnostic biomarker in hepatocellular carcinoma independent of hepatic function","volume":"7","author":"Okajima","year":"2016","journal-title":"Oncotarget"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"44050","DOI":"10.18632\/oncotarget.17211","article-title":"Circulating miR-21 serves as a serum biomarker for hepatocellular carcinoma and correlated with distant metastasis","volume":"8","author":"Guo","year":"2017","journal-title":"Oncotarget"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1111\/hepr.13338","article-title":"Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma","volume":"49","author":"Chuma","year":"2019","journal-title":"Hepatol. Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"529","DOI":"10.3109\/13547500903150771","article-title":"MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma","volume":"14","author":"Yamamoto","year":"2009","journal-title":"Biomarkers"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/j.clinre.2018.12.008","article-title":"Identification of plasma miR-148a as a noninvasive biomarker for hepatocellular carcinoma","volume":"43","author":"Han","year":"2019","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.clinbiochem.2019.01.002","article-title":"Circulating miR-26a, miR-106b, miR-107 and miR-133b stratify hepatocellular carcinoma patients according to their response to transarterial chemoembolization","volume":"65","author":"Ali","year":"2019","journal-title":"Clin. Biochem."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.3346\/jkms.2018.33.e6","article-title":"Plasma MicroRNA-21, 26a, and 29a-3p as Predictive Markers for Treatment Response Following Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma","volume":"33","author":"Kim","year":"2018","journal-title":"J. Korean Med. Sci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/j.clinbiochem.2015.06.019","article-title":"High circulating microRNA-122 expression is a poor prognostic marker in patients with hepatitis B virus-related hepatocellular carcinoma who undergo radiofrequency ablation","volume":"48","author":"Cho","year":"2015","journal-title":"Clin. Biochem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.clinre.2016.09.011","article-title":"Low levels of circulating microRNA-26a\/29a as poor prognostic markers in patients with hepatocellular carcinoma who underwent curative treatment","volume":"41","author":"Cho","year":"2017","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1158\/1078-0432.CCR-16-1464","article-title":"In Hepatocellular Carcinoma miR-221 Modulates Sorafenib Resistance through Inhibition of Caspase-3-Mediated Apoptosis","volume":"23","author":"Fornari","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1053\/j.gastro.2019.01.261","article-title":"Biomarkers Associated With Response to Regorafenib in Patients With Hepatocellular Carcinoma","volume":"156","author":"Teufel","year":"2019","journal-title":"Gastroenterology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/5\/1541\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:30:38Z","timestamp":1760175038000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/9\/5\/1541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,20]]},"references-count":156,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["jcm9051541"],"URL":"https:\/\/doi.org\/10.3390\/jcm9051541","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,20]]}}}