Biomarkers for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The HCC diagnosis is usually achieved by biomarkers, which can also help in prognosis prediction. Furthermore, it might represent certain therapeutic interventions through some combinations of biomarkers. Here, we review on our current understanding of HCC biomarkers.

[1]  T. Muramatsu.  Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases , 2010, Proceedings of the Japan Academy. Series B, Physical and biological sciences.

[2]  P. Tangkijvanich,et al.  Clinical Characteristics and Prognosis of Hepatocellular Carcinoma: Analysis Based on Serum Alpha-fetoprotein Levels , 2000, Journal of clinical gastroenterology.

[3]  H. Aburatani,et al.  Identification of Soluble NH2-Terminal Fragment of Glypican-3 as a Serological Marker for Early-Stage Hepatocellular Carcinoma , 2004, Cancer Research.

[4]  William M. Lee,et al.  Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma. , 2010, Gastroenterology.

[5]  Haifeng Xu,et al.  Value of Quantitative and Qualitative Analyses of Circulating Cell-Free DNA as Diagnostic Tools for Hepatocellular Carcinoma , 2015, Medicine.

[6]  M. Soresi,et al.  Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. , 2003, Anticancer research.

[7]  E. Safwat,et al.  The Value of Serum Midkine Level in Diagnosis of Hepatocellular Carcinoma , 2015, International journal of hepatology.

[8]  J. I. Lee,et al.  Prognosis of hepatocellular carcinoma expressing cytokeratin 19: comparison with other liver cancers. , 2012, World journal of gastroenterology.

[9]  Wanjun Yu,et al.  Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance. , 2011, Biochemical and biophysical research communications.

[10]  J. Bruix,et al.  Cholangiocarcinoma in cirrhosis: Absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma , 2009, Hepatology.

[11]  Hao Xu,et al.  Comparison osteopontin vs AFP for the diagnosis of HCC: a meta-analysis. , 2014, Clinics and research in hepatology and gastroenterology.

[12]  P. Qi,et al.  Serum MicroRNAs as Biomarkers for Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection , 2011, PloS one.

[13]  B. McMahon,et al.  Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: A 16‐year population‐based study , 2000, Hepatology.

[14]  J. Goedert,et al.  The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa , 2004, Hepatology.

[15]  Francesco Donato,et al.  Hepatocellular carcinoma in cirrhosis: incidence and risk factors. , 2004, Gastroenterology.

[16]  M. Kim,et al.  Glypican‐3 is overexpressed in human hepatocellular carcinoma , 2003, Cancer science.

[17]  P. Liaw,et al.  Breast cancer chemotherapy induces the release of cell‐free DNA, a novel procoagulant stimulus , 2011, Journal of thrombosis and haemostasis : JTH.

[18]  B. Debuire,et al.  New perspectives and strategy research biomarkers for hepatocellular carcinoma , 2007, Clinical chemistry and laboratory medicine.

[19]  A. Harris,et al.  Detection of elevated levels of tumour‐associated microRNAs in serum of patients with diffuse large B‐cell lymphoma , 2008, British journal of haematology.

[20]  G. Malaguarnera,et al.  Serum Markers of Hepatocellular Carcinoma , 2010, Digestive Diseases and Sciences.

[21]  B. Vogelstein,et al.  Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry. , 2001, Cancer research.

[22]  P. Pontisso,et al.  Squamous cell carcinoma antigen-IgM is associated with hepatocellular carcinoma in patients with cirrhosis: A prospective study. , 2016, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[23]  J. Marrero,et al.  Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma. , 2009, Gastroenterology.

[24]  S. Fouad,et al.  Plasma Osteopontin Level in Chronic Liver Disease and Hepatocellular Carcinoma , 2015, Hepatitis monthly.

[25]  Zheng Wang,et al.  Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  Xuan Zhang,et al.  Systematic Review and Meta‐Analysis: Circulating miRNAs for Diagnosis of Hepatocellular Carcinoma , 2016, Journal of cellular physiology.

[27]  正敏 新後閑.  Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development , 2010 .

[28]  E. Diamandis,et al.  The sweet and sour of serological glycoprotein tumor biomarker quantification , 2013, BMC Medicine.

[29]  J. Goedert,et al.  Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia. , 2000, Journal of the National Cancer Institute.

[30]  J. Marrero,et al.  Des‐gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients , 2003, Hepatology.

[31]  Wangshu Xu,et al.  RETRACTED ARTICLE: Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels , 2014, Tumor Biology.

[32]  W. Tan,et al.  Circulating MicroRNAs, miR‐21, miR‐122, and miR‐223, in patients with hepatocellular carcinoma or chronic hepatitis , 2011, Molecular Carcinogenesis.

[33]  H. Eguchi,et al.  Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma. , 2012, Journal of hepatology.

[34]  J. Filmus.  The contribution of in vivo manipulation of gene expression to the understanding of the function of glypicans , 2002, Glycoconjugate Journal.

[35]  Y. Nagakawa,et al.  Deregulation of miR‐92a expression is implicated in hepatocellular carcinoma development , 2010, Pathology international.

[36]  Xiaohang Zhao,et al.  Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma , 2012, Carcinogenesis.

[37]  X. Wang,et al.  Evaluation of Midkine as a Diagnostic Serum Biomarker in Hepatocellular Carcinoma , 2013, Clinical Cancer Research.

[38]  P. Pontisso,et al.  Diagnostic and prognostic role of SCCA‐IgM serum levels in hepatocellular carcinoma (HCC) , 2014, Journal of gastroenterology and hepatology.

[39]  M. Sherman,et al.  Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma. , 2009, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[40]  D. Parkin,et al.  Screening for liver cancer: results of a randomised controlled trial in Qidong, China , 2003, Journal of medical screening.

[41]  J. Marrero,et al.  Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3. , 2007, Cancer biomarkers : section A of Disease markers.

[42]  W. Lau,et al.  Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[43]  S. Giordano,et al.  Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis , 2015, Oncotarget.

[44]  Ziding Feng,et al.  Identification of osteopontin as a novel marker for early hepatocellular carcinoma , 2012, Hepatology.

[45]  W. Lau,et al.  Frequent p 15 Promoter Methylation in Tumor and Peripheral Blood from Hepatocellular Carcinoma Patients 1 , 2000 .

[46]  K. Shedden,et al.  Mass-Selected Site-Specific Core-Fucosylation of Serum Proteins in Hepatocellular Carcinoma. , 2015, Journal of proteome research.

[47]  A. Lok,et al.  α‐fetoprotein monitoring in chinese patients with chronic hepatitis B virus infection: Role in the early detection of hepatocellular carcinoma , 1989, Hepatology.

[48]  P. Trerotoli,et al.  SCCA antigen combined with alpha‐fetoprotein as serologic markers of HCC , 2005, International journal of cancer.

[49]  F. Grizzi,et al.  Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma , 2007, Journal of Translational Medicine.

[50]  Ruedi Aebersold,et al.  Mass spectrometric protein maps for biomarker discovery and clinical research , 2013, Expert review of molecular diagnostics.

[51]  W. Alexander,et al.  European Association for the Study of the Liver , 1968 .

[52]  A. Ido,et al.  Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease. , 2011, Oncology reports.

[53]  G. Weber.  The cancer biomarker osteopontin: combination with other markers. , 2011, Cancer genomics & proteomics.

[54]  H. Toyoda,et al.  High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma , 2013, Journal of Gastroenterology.

[55]  V. Mazzaferro,et al.  EASL-EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma European Association for the Study of the Liver ⇑ , European Organisation for Research and Treatment of Cancer , 2012 .

[56]  P. Hainaut,et al.  Ser-249 TP53 and CTNNB1 mutations in circulating free DNA of Egyptian patients with hepatocellular carcinoma versus chronic liver diseases. , 2008, Cancer letters.

[57]  Keigo Saito,et al.  Biomarkers for the early diagnosis of hepatocellular carcinoma. , 2015, World journal of gastroenterology.

[58]  M. Albitar,et al.  Circulating MicroRNAs as Biomarkers for Hepatocellular Carcinoma , 2011, Journal of clinical gastroenterology.

[59]  Chen Li,et al.  Automated immunoassay system for AFP-L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis. , 2009, Analytical biochemistry.

[60]  Bo Li,et al.  Detection of aberrant promoter methylation of GSTP1 in the tumor and serum of Chinese human primary hepatocellular carcinoma patients. , 2006, Clinical biochemistry.

[61]  C. Ricciardelli,et al.  The Role of Annexin A2 in Tumorigenesis and Cancer Progression , 2011, Cancer Microenvironment.

[62]  Cheolju Lee,et al.  Integrated Glycoproteomics Demonstrates Fucosylated Serum Paraoxonase 1 Alterations in Small Cell Lung Cancer , 2013, Molecular & Cellular Proteomics.

[63]  P. Tangkijvanich,et al.  Diagnostic role of serum glypican‐3 in differentiating hepatocellular carcinoma from non‐malignant chronic liver disease and other liver cancers , 2010, Journal of gastroenterology and hepatology.

[64]  L. Terracciano,et al.  Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis , 2007, Hepatology.

[65]  Wei Liu,et al.  Comparison of Serum Tumor Markers for Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma , 2010, The American surgeon.

[66]  Daniel B. Martin,et al.  Circulating microRNAs as stable blood-based markers for cancer detection , 2008, Proceedings of the National Academy of Sciences.

[67]  J. Goedert,et al.  249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma , 2005, Oncogene.

[68]  Masatoshi Kudo,et al.  1398 BRIVANIB VERSUS PLACEBO IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA (HCC) WHO FAILED OR WERE INTOLERANT TO SORAFENIB: RESULTS FROM THE PHASE 3 BRISK-PS STUDY , 2012 .

[69]  G. Bulla,et al.  Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease , 2002, Hepatology.

[70]  Takashi Morita,et al.  γ-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-γ-carboxy prothrombin , 2002 .

[71]  W. Yeo,et al.  High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[72]  S. Satomura,et al.  AFP-L3: a new generation of tumor marker for hepatocellular carcinoma. , 2001, Clinica chimica acta; international journal of clinical chemistry.

[73]  G. Weber,et al.  Interactions between osteopontin and vascular endothelial growth factor: Implications for cancer. , 2015, Biochimica et biophysica acta.

[74]  Ying-yi Zhang,et al.  Prognostic value of cytokeratin 19 in hepatocellular carcinoma: A meta-analysis. , 2015, Clinica chimica acta; international journal of clinical chemistry.

[75]  Minshan Chen,et al.  A blood-based three-gene signature for the non-invasive detection of early human hepatocellular carcinoma. , 2014, European journal of cancer.

[76]  Wei-Wen Xu,et al.  Development of a Clinical Chemiluminescent Immunoassay for Serum GPC3 and Simultaneous Measurements Alone With AFP and CK19 in Diagnosis of Hepatocellular Carcinoma , 2015, Journal of clinical laboratory analysis.

[77]  J. García-Verdugo,et al.  Molecular and Cellular Pathobiology Cancer Research Cell-Free Nucleic Acids Circulating in the Plasma of Colorectal Cancer Patients Induce the Oncogenic Transformation of Susceptible Cultured Cells , 2010 .

[78]  Jeong Min Lee,et al.  Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma , 2010, Hepatology international.

[79]  C. Ding,et al.  Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma. , 2008, Clinical chemistry.

[80]  K. Migita,et al.  Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus , 2010, Journal of Gastroenterology.

[81]  H. Aburatani,et al.  Identification of Soluble NH 2-Terminal Fragment of Glypican-3 as a Serological Marker for Early-Stage Hepatocellular Carcinoma , 2004 .

[82]  Yaping Tian,et al.  Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases , 2011, International journal of cancer.

[83]  H. Otu,et al.  Serum Proteomics and Biomarkers in Hepatocellular Carcinoma and Chronic Liver Disease , 2008, Clinical Cancer Research.

[84]  H. Reeves,et al.  A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease , 2009, BMC Cancer.

[85]  J. Goedert,et al.  Ser-249 p53 Mutations in Plasma DNA of Patients With Hepatocellular Carcinoma From The Gambia. , 2000, Journal of the National Cancer Institute.

[86]  Mary Ann Comunale,et al.  GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma. , 2005, Journal of hepatology.

[87]  B. Shapiro,et al.  Free DNA in the serum of cancer patients and the effect of therapy. , 1977, Cancer research.

[88]  Xiao-jing Yang,et al.  A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study. , 2015, The Lancet. Oncology.

[89]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[90]  H. Whittle,et al.  Ser‐249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa , 2004, International journal of cancer.

[91]  D. Li,et al.  Identification of circulating MicroRNAs as novel potential biomarkers for hepatocellular carcinoma detection: a systematic review and meta-analysis , 2015, Clinical and Translational Oncology.

[92]  H. Toyoda,et al.  Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus , 2011, Journal of Gastroenterology.

[93]  Christian Schulz,et al.  Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis. , 2015, World journal of hepatology.

[94]  L. Qin,et al.  Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies , 2014, Frontiers of Medicine.

[95]  T. Muramatsu.  Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis. , 2002, Journal of biochemistry.

[96]  Y. Kohgo,et al.  gamma-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-gamma-carboxy prothrombin. , 2002, Biochimica et biophysica acta.

[97]  X. Chen,et al.  Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma. , 2010, Cancer research.

[98]  K. Taketa,et al.  Evaluation of tumor markers for the detection of hepatocellular carcinoma in Yangon General Hospital, Myanmar. , 2002, Acta medica Okayama.

[99]  Fu-dong Lv,et al.  CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection , 2016, PloS one.

[100]  Wei Wu,et al.  Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma , 2015, Tumor Biology.