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PMID: 28469485 Published · epublish English Journal Article Review

Biomarkers for Hepatocellular Carcinoma.

Biomarkers in cancer ·Vol. 9 ·2017-00-00 ·Pages 1-9

Lou J, Zhang L, Lv S, Zhang C, Jiang S

Abstract

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.

Keywords
Hepatocellular carcinoma biomarkers diagnosis prognosis
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lou Jiatao
Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Zhang LingFei
Center for RNA Research, State Key Laboratory of Molecular Biology, Chinese Academy of Sciences (CAS), Shanghai, China. | Department of Anatomy, Histology & Embryology, Shanghai Medical College, Fudan University, Shanghai, China.
Lv Shaogang
Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Zhang Chenzi
Department of Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Jiang Shuai
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Conflict of Interest

DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References (95)
95 references, click to expand
  1. Ser-249 TP53 and CTNNB1 mutations in circulating free DNA of Egyptian patients with hepatocellular carcinoma versus chronic liver diseases.
    Cancer Lett. 2008 Jun 18;264(2):201-8 PMID: 18313840
  2. The cancer biomarker osteopontin: combination with other markers.
    Cancer Genomics Proteomics. 2011 Nov-Dec;8(6):263-88 PMID: 22086896
  3. CK19 and Glypican 3 Expression Profiling in the Prognostic Indication for Patients with HCC after Surgical Resection.
    PLoS One. 2016 Mar 15;11(3):e0151501 PMID: 26977595
  4. Alpha-fetoprotein, des-gamma carboxyprothrombin, and lectin-bound alpha-fetoprotein in early hepatocellular carcinoma.
    Gastroenterology. 2009 Jul;137(1):110-8 PMID: 19362088
  5. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels.
    J Clin Gastroenterol. 2000 Dec;31(4):302-8 PMID: 11129271
  6. SCCA antigen combined with alpha-fetoprotein as serologic markers of HCC.
    Int J Cancer. 2005 Nov 10;117(3):506-9 PMID: 15906357
  7. Integrated glycoproteomics demonstrates fucosylated serum paraoxonase 1 alterations in small cell lung cancer.
    Mol Cell Proteomics. 2014 Jan;13(1):30-48 PMID: 24085812
  8. Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC).
    J Gastroenterol Hepatol. 2014 Aug;29(8):1637-44 PMID: 24635038
  9. Expression of GP73, a resident Golgi membrane protein, in viral and nonviral liver disease.
    Hepatology. 2002 Jun;35(6):1431-40 PMID: 12029628
  10. Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma.
    Clin Chem. 2008 Sep;54(9):1528-36 PMID: 18653827
  11. The contribution of in vivo manipulation of gene expression to the understanding of the function of glypicans.
    Glycoconj J. 2002 May-Jun;19(4-5):319-23 PMID: 12975611
  12. gamma-Carboxyglutamic acid content of hepatocellular carcinoma-associated des-gamma-carboxy prothrombin.
    Biochim Biophys Acta. 2002 Apr 24;1586(3):287-98 PMID: 11997080
  13. Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis.
    Hepatology. 2007 Mar;45(3):725-34 PMID: 17326147
  14. The role of annexin A2 in tumorigenesis and cancer progression.
    Cancer Microenviron. 2011 Aug;4(2):199-208 PMID: 21909879
  15. High frequency of promoter hypermethylation of RASSF1A in tumor and plasma of patients with hepatocellular carcinoma.
    Liver Int. 2005 Apr;25(2):266-72 PMID: 15780049
  16. Glypican-3 is overexpressed in human hepatocellular carcinoma.
    Cancer Sci. 2003 Mar;94(3):259-62 PMID: 12824919
  17. Frequent p15 promoter methylation in tumor and peripheral blood from hepatocellular carcinoma patients.
    Clin Cancer Res. 2000 Sep;6(9):3516-21 PMID: 10999738
  18. Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies.
    Front Med. 2014 Mar;8(1):24-32 PMID: 24464486
  19. Utility of Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxy prothrombin, alone or in combination, as biomarkers for hepatocellular carcinoma.
    Clin Gastroenterol Hepatol. 2009 Jan;7(1):104-13 PMID: 18849011
  20. The sweet and sour of serological glycoprotein tumor biomarker quantification.
    BMC Med. 2013 Feb 07;11:31 PMID: 23390961
  21. Serological AFP/Golgi protein 73 could be a new diagnostic parameter of hepatic diseases.
    Int J Cancer. 2011 Oct 15;129(8):1923-31 PMID: 21140449
  22. Breast cancer chemotherapy induces the release of cell-free DNA, a novel procoagulant stimulus.
    J Thromb Haemost. 2011 Nov;9(11):2313-21 PMID: 21838758
  23. Predictive value of tumor markers for hepatocarcinogenesis in patients with hepatitis C virus.
    J Gastroenterol. 2011 Apr;46(4):536-44 PMID: 21132575
  24. Automated immunoassay system for AFP-L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis.
    Anal Biochem. 2009 May 15;388(2):306-11 PMID: 19250915
  25. Serum microRNA profiles serve as novel biomarkers for HBV infection and diagnosis of HBV-positive hepatocarcinoma.
    Cancer Res. 2010 Dec 1;70(23):9798-807 PMID: 21098710
  26. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases.
    Cell Res. 2008 Oct;18(10):997-1006 PMID: 18766170
  27. A blood-based three-gene signature for the non-invasive detection of early human hepatocellular carcinoma.
    Eur J Cancer. 2014 Mar;50(5):928-36 PMID: 24332572
  28. Highly sensitive lens culinaris agglutinin-reactive α-fetoprotein is useful for early detection of hepatocellular carcinoma in patients with chronic liver disease.
    Oncol Rep. 2011 Nov;26(5):1227-33 PMID: 21874252
  29. GP73, a resident Golgi glycoprotein, is a novel serum marker for hepatocellular carcinoma.
    J Hepatol. 2005 Dec;43(6):1007-12 PMID: 16137783
  30. Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus.
    J Gastroenterol. 2011 Jan;46(1):92-100 PMID: 20711614
  31. Up-regulation of annexin A2 expression predicates advanced clinicopathological features and poor prognosis in hepatocellular carcinoma.
    Tumour Biol. 2015 Dec;36(12):9373-83 PMID: 26109000
  32. Annexin A2 is a discriminative serological candidate in early hepatocellular carcinoma.
    Carcinogenesis. 2013 Mar;34(3):595-604 PMID: 23188673
  33. Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis.
    J Biochem. 2002 Sep;132(3):359-71 PMID: 12204104
  34. Identification of osteopontin as a novel marker for early hepatocellular carcinoma.
    Hepatology. 2012 Feb;55(2):483-90 PMID: 21953299
  35. Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma.
    Anticancer Res. 2003 Mar-Apr;23(2C):1747-53 PMID: 12820452
  36. Cholangiocarcinoma in cirrhosis: absence of contrast washout in delayed phases by magnetic resonance imaging avoids misdiagnosis of hepatocellular carcinoma.
    Hepatology. 2009 Sep;50(3):791-8 PMID: 19610049
  37. Comparison osteopontin vs AFP for the diagnosis of HCC: a meta-analysis.
    Clin Res Hepatol Gastroenterol. 2014 Dec;38(6):706-14 PMID: 25034355
  38. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma.
    J Clin Oncol. 2011 Dec 20;29(36):4781-8 PMID: 22105822
  39. 249(ser) TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma.
    Oncogene. 2005 Sep 1;24(38):5858-67 PMID: 16007211
  40. The value of serum midkine level in diagnosis of hepatocellular carcinoma.
    Int J Hepatol. 2015;2015:146389 PMID: 25737783
  41. Serum markers of hepatocellular carcinoma.
    Semin Liver Dis. 2006 Nov;26(4):385-90 PMID: 17051452
  42. Mass-Selected Site-Specific Core-Fucosylation of Serum Proteins in Hepatocellular Carcinoma.
    J Proteome Res. 2015 Nov 6;14 (11):4876-84 PMID: 26403951
  43. Serum microRNAs as biomarkers for hepatocellular carcinoma in Chinese patients with chronic hepatitis B virus infection.
    PLoS One. 2011;6(12):e28486 PMID: 22174818
  44. Identification of circulating MicroRNAs as novel potential biomarkers for hepatocellular carcinoma detection: a systematic review and meta-analysis.
    Clin Transl Oncol. 2015 Sep;17(9):684-93 PMID: 25956842
  45. Hepatocellular carcinoma in cirrhosis: incidence and risk factors.
    Gastroenterology. 2004 Nov;127(5 Suppl 1):S35-50 PMID: 15508101
  46. New perspectives and strategy research biomarkers for hepatocellular carcinoma.
    Clin Chem Lab Med. 2007;45(9):1169-79 PMID: 17635075
  47. Mass spectrometric protein maps for biomarker discovery and clinical research.
    Expert Rev Mol Diagn. 2013 Nov;13(8):811-25 PMID: 24138574
  48. Detection of aberrant promoter methylation of GSTP1 in the tumor and serum of Chinese human primary hepatocellular carcinoma patients.
    Clin Biochem. 2006 Apr;39(4):344-8 PMID: 16527261
  49. The Gambia Liver Cancer Study: Infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa.
    Hepatology. 2004 Jan;39(1):211-9 PMID: 14752840
  50. Comparison of serum tumor markers for intrahepatic cholangiocarcinoma and hepatocellular carcinoma.
    Am Surg. 2010 Nov;76(11):1210-3 PMID: 21140686
  51. Circulating microRNAs as biomarkers for hepatocellular carcinoma.
    J Clin Gastroenterol. 2011 Apr;45(4):355-60 PMID: 21278583
  52. Midkine, a heparin-binding cytokine with multiple roles in development, repair and diseases.
    Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(4):410-25 PMID: 20431264
  53. Serum proteomics and biomarkers in hepatocellular carcinoma and chronic liver disease.
    Clin Cancer Res. 2008 Jan 15;14(2):470-7 PMID: 18223221
  54. Identification of soluble NH2-terminal fragment of glypican-3 as a serological marker for early-stage hepatocellular carcinoma.
    Cancer Res. 2004 Apr 1;64(7):2418-23 PMID: 15059894
  55. Ser-249 p53 mutations in plasma DNA of patients with hepatocellular carcinoma from The Gambia.
    J Natl Cancer Inst. 2000 Jan 19;92(2):148-53 PMID: 10639517
  56. Prognosis of hepatocellular carcinoma expressing cytokeratin 19: comparison with other liver cancers.
    World J Gastroenterol. 2012 Sep 14;18(34):4751-7 PMID: 23002345
  57. Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study.
    Hepatology. 2000 Oct;32(4 Pt 1):842-6 PMID: 11003632
  58. Prognostic value of cytokeratin 19 in hepatocellular carcinoma: A meta-analysis.
    Clin Chim Acta. 2015 Aug 25;448:161-9 PMID: 26164382
  59. Plasma Osteopontin Level in Chronic Liver Disease and Hepatocellular Carcinoma.
    Hepat Mon. 2015 Sep 01;15(9):e30753 PMID: 26500684
  60. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma.
    Br J Haematol. 2008 May;141(5):672-5 PMID: 18318758
  61. Current biomarkers for hepatocellular carcinoma: Surveillance, diagnosis and prediction of prognosis.
    World J Hepatol. 2015 Feb 27;7(2):139-49 PMID: 25729470
  62. Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3.
    Cancer Biomark. 2007;3(2):79-87 PMID: 17522429
  63. Systematic Review and Meta-Analysis: Circulating miRNAs for Diagnosis of Hepatocellular Carcinoma.
    J Cell Physiol. 2016 Feb;231(2):328-35 PMID: 26291451
  64. Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers.
    J Gastroenterol Hepatol. 2010 Jan;25(1):129-37 PMID: 19793164
  65. Cytokeratin-19 positivity is acquired along cancer progression and does not predict cell origin in rat hepatocarcinogenesis.
    Oncotarget. 2015 Nov 17;6(36):38749-63 PMID: 26452031
  66. Cell-free nucleic acids circulating in the plasma of colorectal cancer patients induce the oncogenic transformation of susceptible cultured cells.
    Cancer Res. 2010 Jan 15;70(2):560-7 PMID: 20068178
  67. Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry.
    Cancer Res. 2001 Jan 1;61(1):33-5 PMID: 11196182
  68. Expression of serum miR-221 in human hepatocellular carcinoma and its prognostic significance.
    Biochem Biophys Res Commun. 2011 Mar 4;406(1):70-3 PMID: 21295551
  69. A serum microRNA classifier for early detection of hepatocellular carcinoma: a multicentre, retrospective, longitudinal biomarker identification study with a nested case-control study.
    Lancet Oncol. 2015 Jul;16(7):804-15 PMID: 26088272
  70. Biomarkers for the early diagnosis of hepatocellular carcinoma.
    World J Gastroenterol. 2015 Oct 7;21(37):10573-83 PMID: 26457017
  71. Value of quantitative and qualitative analyses of circulating cell-free DNA as diagnostic tools for hepatocellular carcinoma: a meta-analysis.
    Medicine (Baltimore). 2015 Apr;94(14):e722 PMID: 25860220
  72. Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels.
    Tumour Biol. 2014 Dec;35(12):12069-74 PMID: 25209179
  73. Squamous cell carcinoma antigen-IgM is associated with hepatocellular carcinoma in patients with cirrhosis: A prospective study.
    Dig Liver Dis. 2016 Feb;48(2):197-202 PMID: 26614642
  74. Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients.
    Cancer Res. 1999 Jan 1;59(1):71-3 PMID: 9892188
  75. Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma.
    Hepatol Int. 2010 Mar 18;4(2):439-74 PMID: 20827404
  76. Circulating microRNA-21 as a novel biomarker for hepatocellular carcinoma.
    J Hepatol. 2012 Jan;56(1):167-75 PMID: 21749846
  77. Ser-249TP53 mutation in tumour and plasma DNA of hepatocellular carcinoma patients from a high incidence area in the Gambia, West Africa.
    Int J Cancer. 2004 Jun 20;110(3):374-9 PMID: 15095302
  78. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients.
    Hepatology. 2003 May;37(5):1114-21 PMID: 12717392
  79. Interactions between osteopontin and vascular endothelial growth factor: Implications for cancer.
    Biochim Biophys Acta. 2015 Apr;1855(2):202-22 PMID: 25732057
  80. AFP-L3: a new generation of tumor marker for hepatocellular carcinoma.
    Clin Chim Acta. 2001 Nov;313(1-2):15-9 PMID: 11694234
  81. Circulating microRNAs, miR-21, miR-122, and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis.
    Mol Carcinog. 2011 Feb;50(2):136-42 PMID: 21229610
  82. A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease.
    BMC Cancer. 2009 Aug 05;9:271 PMID: 19656391
  83. Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma.
    J Transl Med. 2007 Jan 23;5:3 PMID: 17244360
  84. Deregulation of miR-92a expression is implicated in hepatocellular carcinoma development.
    Pathol Int. 2010 May;60(5):351-7 PMID: 20518884
  85. alpha-Fetoprotein monitoring in Chinese patients with chronic hepatitis B virus infection: role in the early detection of hepatocellular carcinoma.
    Hepatology. 1989 Jan;9(1):110-5 PMID: 2461890
  86. Free DNA in the serum of cancer patients and the effect of therapy.
    Cancer Res. 1977 Mar;37(3):646-50 PMID: 837366
  87. Circulating microRNAs as stable blood-based markers for cancer detection.
    Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8 PMID: 18663219
  88. Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma.
    Clin Cancer Res. 2013 Jul 15;19(14):3944-54 PMID: 23719264
  89. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.
    J Hepatol. 2012 Apr;56(4):908-43 PMID: 22424438
  90. High-sensitivity Lens culinaris agglutinin-reactive alpha-fetoprotein assay predicts early detection of hepatocellular carcinoma.
    J Gastroenterol. 2014 Mar;49(3):555-63 PMID: 24057163
  91. Embryonic stem cell-derived dendritic cells expressing glypican-3, a recently identified oncofetal antigen, induce protective immunity against highly metastatic mouse melanoma, B16-F10.
    Cancer Res. 2006 Feb 15;66(4):2414-22 PMID: 16489048
  92. Evaluation of tumor markers for the detection of hepatocellular carcinoma in Yangon General Hospital, Myanmar.
    Acta Med Okayama. 2002 Dec;56(6):317-20 PMID: 12685861
  93. Development of a clinical chemiluminescent immunoassay for serum GPC3 and simultaneous measurements alone with AFP and CK19 in diagnosis of hepatocellular carcinoma.
    J Clin Lab Anal. 2015 Mar;29(2):85-93 PMID: 24687454
  94. Screening for liver cancer: results of a randomised controlled trial in Qidong, China.
    J Med Screen. 2003;10(4):204-9 PMID: 14738659
  95. Des-gamma-carboxy prothrombin and alpha-fetoprotein as biomarkers for the early detection of hepatocellular carcinoma.
    Gastroenterology. 2010 Feb;138(2):493-502 PMID: 19852963
Article Info
Journal
Biomarkers in cancer
Abbr.
Biomark Cancer
ISSN
1179-299X
DOI
10.1177/1179299X16684640
Published
2017-00-00
Epub
2017-00-28
Pages
1-9
Language
English
Region
United States
NLM ID
101533144
PMCID
PMC5345949
External Links
PubMed source DOI: 10.1177/1179299X16684640 PMC Full Text
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