Skip to main content
SpringerLink
Log in

Perspectives in Biochemical Staging of Hepatocellular Carcinoma Over the Current Microscopical Methodology

  • Living reference work entry
  • First Online:
Handbook of Cancer and Immunology

  • 65 Accesses

Abstract

Hepatocellular carcinoma (HCC) is considered the third main cause of cancer-related deaths globally. Comparing with other tumors, survival of HCC patients is consistent with the extent of the tumor besides underlying liver condition and functional reserve of the liver. HCC displays significant institutional and geographic variations from risk factors to management over the world. Despite various HCC staging systems that have been developed, each system shows its benefits and limitations. Histological staging (grading) plays a vital role in reflecting the biological behavior of solid tumors. Circulating cell-free DNA is only is useful in the early detection of HCC. The same is applicable for many proteins as AFP-L3, AFP, DCP, osteopontin (OPN), glypican-3 (GPC3), midkine (MDK), annexin A2, GP73, soluble urokinase plasminogen activator receptor, squamous cell carcinoma antigen, and thioredoxin which were reported to have value only for the early diagnostic biomarkers for HCC. However, it exhibits various limitations, including invasiveness and patient acceptance, which always restrict its application. In this chapter, we try to discuss the possible different biochemical markers that may help in evaluating HCC staging and prognosis and hopefully replacing the currently used invasive histological staging systems.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Abdel-Hamid NM (2009) Premalignant variations in extracellular matrix composition in chemically induced hepatocellular carcinoma in rats. J Membr Biol 230(3):155–162. ISSN 0022-2631

    Article  CAS  Google Scholar 

  • Abdel-Hamid NM, Abdullah AH (2019) Serum histamine and acetylcholine variations as new noninvasive biochemical markers in staging of experimental hepatocellular carcinoma. Clin Exp Med 19(1):115–120. ISSN 1591-8890

    Article  CAS  Google Scholar 

  • Abdel-Hamid NM, El-Moselhy MA, Fawzy MA (2012) Novel panel of early diagnostic markers for experimental hepatocellular carcinoma. Health 2:14–18

    Article  Google Scholar 

  • Abdel-Hamid NM et al (2016) Serum serotonin as unexpected potential marker for staging of experimental hepatocellular carcinoma. Biomed Pharmacother 83:407–411. ISSN 0753-3322

    Article  CAS  Google Scholar 

  • Aceto N et al (2014) Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell 158(5):1110–1122. ISSN 0092-8674

    Article  CAS  Google Scholar 

  • Ahmad MS et al (2019) Current status regarding tumour progression, surveillance, diagnosis, staging, and treatment of HCC: a literature review. J Gastroenterol Hepatol Res 8(2):2841–2852. ISSN 2224-6509

    Article  CAS  Google Scholar 

  • Ahn JC et al (2021) Detection of circulating tumor cells and their implications as a biomarker for diagnosis, prognostication, and therapeutic monitoring in hepatocellular carcinoma. Hepatology 73(1):422–436. ISSN 0270-9139

    Article  Google Scholar 

  • Borel F, Konstantinova P, Jansen PL (2012) Diagnostic and therapeutic potential of miRNA signatures in patients with hepatocellular carcinoma. J Hepatol 56(6):1371–1383. ISSN 0168-8278

    Article  CAS  Google Scholar 

  • Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3):1020–1022. ISSN 1527-3350

    Article  Google Scholar 

  • Bruix J et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. J Hepatol 35(3):421–430. ISSN 0168-8278

    Article  CAS  Google Scholar 

  • Burt AD et al (2018) Data set for the reporting of intrahepatic cholangiocarcinoma, perihilar cholangiocarcinoma and hepatocellular carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR). Histopathology 73(3):369–385. ISSN 0309-0167

    Article  Google Scholar 

  • Caviglia GP et al (2016) Highly sensitive alpha-fetoprotein, Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein and des-gamma-carboxyprothrombin for hepatocellular carcinoma detection. Hepatol Res 46(3):E130–E135. ISSN 1386-6346 (Print) 1386-6346

    Article  CAS  Google Scholar 

  • Chen C, Jeng L, Huang S (2007) Lymphoepithelioma-like hepatocellular carcinoma. Chang Gung Med J 30(2):172. ISSN 0255-8270

    Google Scholar 

  • Chen X et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006. ISSN 1748-7838 (Electronic) 1001-0602 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/18766170

    Article  CAS  Google Scholar 

  • Chen R et al (2019) Exosomes in hepatocellular carcinoma: a new horizon. Cell Commun Signal 17(1):1. ISSN 1478-811X (Electronic) 1478-811X (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/30616541

    Article  Google Scholar 

  • Chevret S et al (1999) A new prognostic classification for predicting survival in patients with hepatocellular carcinoma. J Hepatol 31(1):133–141. ISSN 0168-8278

    Article  CAS  Google Scholar 

  • Clavien PA et al (2012) Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 13(1):e11–e22. ISSN 1470-2045 (Print) 1470-2045

    Article  Google Scholar 

  • CLIP Investigators (1998) A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28(3):751–755. ISSN 0270-9139

    Article  Google Scholar 

  • Court CM et al (2018) A novel multimarker assay for the phenotypic profiling of circulating tumor cells in hepatocellular carcinoma. Liver Transpl 24(7):946–960. ISSN 1527-6465

    Article  Google Scholar 

  • Cox IJ et al (2016) Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: a biomarker corroboration study. World J Gastroenterol 22(16):4191–4200. ISSN 2219-2840 (Electronic) 1007-9327 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/27122669

    Article  CAS  Google Scholar 

  • Daniele B et al (2004) Alpha-fetoprotein and ultrasonography screening for hepatocellular carcinoma. Gastroenterology 127(5 Suppl 1):S108–S112. ISSN 0016-5085 (Print) 0016-5085

    Article  Google Scholar 

  • Diaz LA Jr, Bardelli A (2014) Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 32(6):579

    Article  Google Scholar 

  • Ducreux M et al (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56(4):908–943

    Article  Google Scholar 

  • Edmondson HA, Steiner PE (1954) Primary carcinoma of the liver. A study of 100 cases among 48,900 necropsies. Cancer 7(3):462–503. ISSN 0008-543X

    Article  CAS  Google Scholar 

  • Fan ST et al (2011) Prediction of posthepatectomy recurrence of hepatocellular carcinoma by circulating cancer stem cells: a prospective study. Ann Surg 254(4):569–576. ISSN 0003-4932

    Article  Google Scholar 

  • Fan JL et al (2015) Circulating tumor cells for predicting the prognostic of patients with hepatocellular carcinoma: a meta analysis. Cell Physiol Biochem 37(2):629–640. ISSN 1015-8987

    Article  CAS  Google Scholar 

  • Farinati F et al (2016) Development and validation of a new prognostic system for patients with hepatocellular carcinoma. PLoS Med 13(4):e1002006. ISSN 1549-1277

    Article  Google Scholar 

  • Fatourou E et al (2015) Keratin 19 protein expression is an independent predictor of survival in human hepatocellular carcinoma. Eur J Gastroenterol Hepatol 27(9):1094–1102. ISSN 0954-691X

    Article  CAS  Google Scholar 

  • Gomaa AI et al (2009) Diagnosis of hepatocellular carcinoma. World J Gastroenterol 15(11):1301–1314. ISSN 1007-9327 (Print) 1007-9327

    Article  Google Scholar 

  • Habli Z et al (2020) Circulating tumor cell detection technologies and clinical utility: challenges and opportunities. Cancers 12(7):1930

    Article  CAS  Google Scholar 

  • Heimbach JK et al (2018) AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 67(1):358–380. ISSN 0270-9139

    Article  Google Scholar 

  • Hsu CY et al (2010) A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol 53(1):108–117. ISSN 0168-8278

    Article  Google Scholar 

  • Hung J-H et al (2018) MicroRNA-224 down-regulates glycine N-methyltransferase gene expression in hepatocellular carcinoma. Sci Rep 8(1):1–14. ISSN 2045-2322.

    Article  Google Scholar 

  • Ikai I et al (2006) A modified Japan Integrated Stage score for prognostic assessment in patients with hepatocellular carcinoma. J Gastroenterol 41(9):884–892. ISSN 0944-1174 (Print) 0944-1174

    Article  Google Scholar 

  • Judson PL et al (2003) Preoperative detection of peripherally circulating cancer cells and its prognostic significance in ovarian cancer. Gynecol Oncol 91(2):389–394. ISSN 0090-8258

    Article  Google Scholar 

  • Karademir S (2018) Staging of hepatocellular carcinoma. Hepatoma Res 4:58. ISSN 2454-2520. Available at: https://doi.org/10.20517/2394-5079.2018.40

    Article  Google Scholar 

  • Karuthan SR et al (2021) Barcelona Clinic Liver Cancer and Hong Kong Liver Cancer staging systems for prediction of survival among hepatocellular carcinoma patients. Med J Malaysia 76(2):199–204. ISSN 0300-5283 (Print) 0300-5283

    CAS  Google Scholar 

  • Kelley RK et al (2015) Circulating tumor cells in hepatocellular carcinoma: a pilot study of detection, enumeration, and next-generation sequencing in cases and controls. BMC Cancer 15:206. ISSN 1471-2407

    Article  Google Scholar 

  • Kitai S et al (2008) A new prognostic staging system for hepatocellular carcinoma: value of the biomarker combined Japan integrated staging score. Intervirology 51(Suppl 1):86–94. ISSN 0300-5526

    Article  CAS  Google Scholar 

  • Klein WM et al (2005) Primary liver carcinoma arising in people younger than 30 years. Am J Clin Pathol 124(4):512–518. ISSN 1943-7722

    Article  Google Scholar 

  • Kudo M, Chung H, Osaki Y (2003) Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging score (JIS score). J Gastroenterol 38(3):207–215. ISSN 0944-1174 (Print) 0944-1174

    Article  Google Scholar 

  • Leung TW et al (2002) Construction of the Chinese University Prognostic Index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system, and the Cancer of the Liver Italian Program staging system: a study based on 926 patients. Cancer 94(6):1760–1769. ISSN 0008-543X (Print) 0008-543x

    Article  Google Scholar 

  • Liang Q et al (2016) Phenotypic characterization analysis of human hepatocarcinoma by urine metabolomics approach. Sci Rep 6:19763. ISSN 2045-2322 (Electronic) 2045-2322 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/26805550

    Article  CAS  Google Scholar 

  • Liu Y et al (2014) NMR and LC/MS-based global metabolomics to identify serum biomarkers differentiating hepatocellular carcinoma from liver cirrhosis. Int J Cancer 135(3):658–668. ISSN 1097-0215 (Electronic) 0020-7136 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/24382646

    Article  CAS  Google Scholar 

  • Liu H-Y et al (2015) Improved method increases sensitivity for circulating hepatocellular carcinoma cells. World J Gastroenterol: WJG 21(10):2918

    Article  Google Scholar 

  • Liu XN et al (2019) Multiple “Omics” data-based biomarker screening for hepatocellular carcinoma diagnosis. World J Gastroenterol 25(30):4199–4212. ISSN 2219-2840 (Electronic) 1007-9327 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/31435173

    Article  CAS  Google Scholar 

  • Llovet JM, Brú C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19(3):329–338. ISSN 0272-8087 (Print) 0272-8087

    Article  CAS  Google Scholar 

  • Llovet JM et al (2016) Hepatocellular carcinoma. Nat Rev Dis Primers 2:16018. ISSN 2056-676x

    Article  Google Scholar 

  • Maida M et al (2014) Staging systems of hepatocellular carcinoma: a review of literature. World J Gastroenterol: WJG 20(15):4141

    Article  Google Scholar 

  • Mann J, Reeves HL, Feldstein AE (2018) Liquid biopsy for liver diseases. Gut 67(12):2204–2212. ISSN 0017-5749

    Article  CAS  Google Scholar 

  • Marrero JA, Kudo M, Bronowicki JP (2010) The challenge of prognosis and staging for hepatocellular carcinoma. Oncologist 15(Suppl 4):23–33. ISSN 1083-7159

    Article  CAS  Google Scholar 

  • Marrero JA et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 68(2):723–750. ISSN 1527-3350

    Article  Google Scholar 

  • Martins-Filho SN, Alves VAF (2019) The strengths and weaknesses of gross and histopathological evaluation in hepatocellular carcinoma: a brief review. Surg Exp Pathol 2(1):23. ISSN 2520-8454. Available at: https://doi.org/10.1186/s42047-019-0047-6

    Article  Google Scholar 

  • Martins-Filho SN et al (2017) Histological grading of hepatocellular carcinoma—a systematic review of literature. Front Med 4:193. ISSN 2296-858X. Available at: https://www.frontiersin.org/article/10.3389/fmed.2017.00193

    Article  Google Scholar 

  • Martins-Filho SN et al (2019) A phenotypical map of disseminated hepatocellular carcinoma suggests clonal constraints in metastatic sites. Histopathology 74(5):718–730. ISSN 0309-0167

    Article  Google Scholar 

  • Matsuda Y et al (1999) p16(INK4) is inactivated by extensive CpG methylation in human hepatocellular carcinoma. Gastroenterology 116(2):394–400. ISSN 0016-5085 (Print) 0016-5085 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/9922321

    Article  CAS  Google Scholar 

  • Miller MC, Doyle GV, Terstappen LW (2010) Significance of circulating tumor cells detected by the CellSearch system in patients with metastatic breast colorectal and prostate cancer. J Oncol 2010:617421. ISSN 1687-8450

    Article  Google Scholar 

  • Mohamed AA et al (2017) MicroRNAs and clinical implications in hepatocellular carcinoma. World J Hepatol 9(23):1001

    Article  Google Scholar 

  • Nocito A et al (2007) Serotonin mediates oxidative stress and mitochondrial toxicity in a murine model of nonalcoholic steatohepatitis. Gastroenterology 133(2):608–618. ISSN 0016-5085 (Print) 0016-5085

    Article  CAS  Google Scholar 

  • Okuda K et al (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment study of 850 patients. Cancer 56(4):918–928. ISSN 0008-543X

    Article  CAS  Google Scholar 

  • Pang Y et al (2018) Dual-selective and dual-enhanced SERS nanoprobes strategy for circulating hepatocellular carcinoma cells detection. Chem Eur J 24(27):7060–7067. ISSN 0947-6539

    Article  CAS  Google Scholar 

  • Pons F, Varela M, Llovet JM (2005) Staging systems in hepatocellular carcinoma. HPB 7(1):35–41. ISSN 1365-182X

    Article  Google Scholar 

  • Poon RT et al (2004) Prognostic significance of serum vascular endothelial growth factor and endostatin in patients with hepatocellular carcinoma. Br J Surg 91(10):1354–1360. ISSN 0007-1323 (Print) 0007-1323

    Article  CAS  Google Scholar 

  • Quaglia A (2018) Hepatocellular carcinoma: a review of diagnostic challenges for the pathologist. J Hepatocell Carcinoma 5:99

    Article  CAS  Google Scholar 

  • Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383. ISSN 1540-8140 (Electronic) 0021-9525 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/23420871

    Article  CAS  Google Scholar 

  • Rashed WM et al (2020) Hepatocellular carcinoma (HCC) in Egypt: a comprehensive overview. J Egypt Natl Canc Inst 32(1):5. ISSN 2589-0409. Available at: https://doi.org/10.1186/s43046-020-0016-x

    Article  Google Scholar 

  • Rimassa L et al (2018) Tivantinib for second-line treatment of MET-high, advanced hepatocellular carcinoma (METIV-HCC): a final analysis of a phase 3, randomised, placebo-controlled study. Lancet Oncol 19(5):682–693. ISSN 1470-2045

    Article  CAS  Google Scholar 

  • Roayaie S et al (2009) A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology 137(3):850–855. ISSN 0016-5085

    Article  Google Scholar 

  • Roncalli M et al (2002) Methylation framework of cell cycle gene inhibitors in cirrhosis and associated hepatocellular carcinoma. Hepatology 36(2):427–432. ISSN 0270-9139 (Print) 0270-9139 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/12143052

    Article  CAS  Google Scholar 

  • Salomao M et al (2010) Steatohepatitic hepatocellular carcinoma (SH-HCC): a distinctive histological variant of HCC in hepatitis C virus-related cirrhosis with associated NAFLD/NASH. Am J Surg Pathol 34(11):1630–1636. ISSN 0147-5185

    Article  Google Scholar 

  • Schlageter M et al (2014) Histopathology of hepatocellular carcinoma. World J Gastroenterol 20(43):15955–15964. ISSN 1007-9327

    Article  Google Scholar 

  • Schulze K et al (2013) Presence of EpCAM-positive circulating tumor cells as biomarker for systemic disease strongly correlates to survival in patients with hepatocellular carcinoma. Int J Cancer 133(9):2165–2171. ISSN 0020-7136

    Article  CAS  Google Scholar 

  • Seeff LB et al (2010) Complication rate of percutaneous liver biopsies among persons with advanced chronic liver disease in the HALT-C trial. Clin Gastroenterol Hepatol 8(10):877–883. ISSN 1542-3565

    Article  Google Scholar 

  • Shen J et al (2018) High epithelial cell adhesion molecule–positive circulating tumor cell count predicts poor survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoembolization. J Vasc Interv Radiol 29(12):1678–1684. ISSN 1051-0443

    Article  Google Scholar 

  • Soll C et al (2010) Serotonin promotes tumor growth in human hepatocellular cancer. Hepatology 51(4):1244–1254. ISSN 0270-9139

    Article  CAS  Google Scholar 

  • Subramaniam S, Kelley RK, Venook AP (2013) A review of hepatocellular carcinoma (HCC) staging systems. Chin Clin Oncol 2(4):33–33. ISSN 2304-3865

    Google Scholar 

  • Swanson BJ et al (2015) A triple stain of reticulin, glypican-3, and glutamine synthetase: a useful aid in the diagnosis of liver lesions. Arch Pathol Lab Med 139(4):537–542. ISSN 1543-2165

    Article  CAS  Google Scholar 

  • Tang JC et al (2016) Circulating tumor DNA in hepatocellular carcinoma: trends and challenges. Cell Biosci 6:32. ISSN 2045-3701 (Print) 2045-3701 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/27182434

    Article  Google Scholar 

  • Tateishi R et al (2005) Proposal of a new prognostic model for hepatocellular carcinoma: an analysis of 403 patients. Gut 54(3):419–425. ISSN 0017-5749 (Print) 0017-5749

    Article  CAS  Google Scholar 

  • Tchou JC et al (2000) GSTP1 CpG island DNA hypermethylation in hepatocellular carcinomas. Int J Oncol 16(4):663–676. ISSN 1019-6439 (Print) 1019-6439 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/10717233

    CAS  Google Scholar 

  • Toffanin S et al (2011) MicroRNA-based classification of hepatocellular carcinoma and oncogenic role of miR-517a. Gastroenterology 140(5):1618–1628.e16. ISSN 0016-5085

    Article  CAS  Google Scholar 

  • Tokumitsu Y, Nagano H (2016) Current HCC staging systems: their uses and limitations. In: Carr B (ed) Hepatocellular carcinoma. Springer, pp 425–442

    Chapter  Google Scholar 

  • Torbenson M, Schirmacher P (2015) Liver cancer biopsy–back to the future?!: Wiley Online Library. Hepatology 61:431–433

    Article  Google Scholar 

  • Toyoda H et al (2006) Staging hepatocellular carcinoma by a novel scoring system (BALAD score) based on serum markers. Clin Gastroenterol Hepatol 4(12):1528–1536. ISSN 1542-3565 (Print) 1542-3565

    Article  CAS  Google Scholar 

  • Toyoda H et al (2015) Tumor markers for hepatocellular carcinoma: simple and significant predictors of outcome in patients with HCC. Liver Cancer 4(2):126–136. ISSN 2235-1795. Available at: https://www.karger.com/DOI/10.1159/000367735

    Article  CAS  Google Scholar 

  • Wang P-X, Cheng J-W, Yang X-R (2020) Detection of circulating tumor cells in hepatocellular carcinoma: applications in diagnosis, prognosis prediction and personalized treatment. Hepatoma Res 6:61. ISSN 2454-2520. Available at: https://doi.org/10.20517/2394-5079.2020.55

    CAS  Google Scholar 

  • Washington K (2010) 7th edition of the AJCC cancer staging manual: stomach. Ann Surg Oncol 17(12):3077–3079. ISSN 1534-4681

    Article  Google Scholar 

  • Wee A, Sampatanukul P (2015) Cytohistology of hepatocellular carcinoma. Diagn Histopathol 21(12):470–480. ISSN 1756-2317

    Article  Google Scholar 

  • Wei R et al (2013) Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma. Clin Cancer Res 19(17):4780–4791. ISSN 1078-0432

    Article  CAS  Google Scholar 

  • Went PT et al (2004) Frequent EpCam protein expression in human carcinomas. Hum Pathol 35(1):122–128. ISSN 0046-8177

    Article  CAS  Google Scholar 

  • Wishart DS (2007) Human metabolome database: completing the “human parts list”. Pharmacogenomics 8(7):683–686. ISSN 1744-8042 (Electronic) 1462-2416 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/18240899

    Article  Google Scholar 

  • Wong QWL et al (2008) MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology 135(1):257–269. ISSN 0016-5085

    Article  CAS  Google Scholar 

  • World Health Organization (2010) World Health Organization classification of tumours by International Agency for Research on Cancer. WHO classification of tumours of the digestive system. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • Xu W et al (2011) Isolation of circulating tumor cells in patients with hepatocellular carcinoma using a novel cell separation strategy. Clin Cancer Res 17(11):3783–3793. ISSN 1078-0432

    Article  Google Scholar 

  • Xu WJ et al (2014) Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumour Biol 35(12):12069–12074. ISSN 1423-0380 (Electronic) 1010-4283 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/25209179

    Article  CAS  Google Scholar 

  • Yanaihara N et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9(3):189–198. ISSN 1535-6108

    Article  CAS  Google Scholar 

  • Yang JD et al (2012) Model to estimate survival in ambulatory patients with hepatocellular carcinoma. Hepatology 56(2):614–621. ISSN 0270-9139 (Print) 0270-9139

    Article  Google Scholar 

  • Yau T et al (2014) Development of Hong Kong Liver Cancer staging system with treatment stratification for patients with hepatocellular carcinoma. Gastroenterology 146(7):1691–700.e3. ISSN 0016-5085

    Article  Google Scholar 

  • Yerukala Sathipati S, Ho S-Y (2020) Novel miRNA signature for predicting the stage of hepatocellular carcinoma. Sci Rep 10(1):14452. ISSN 2045-2322. Available at: https://doi.org/10.1038/s41598-020-71324-z

    Article  CAS  Google Scholar 

  • Yi X, Yu S, Bao Y (2013) Alpha-fetoprotein-L3 in hepatocellular carcinoma: a meta-analysis. Clin Chim Acta 425:212–220. ISSN 0009-8981

    Article  CAS  Google Scholar 

  • Yuen MF, Lai CL (2005) Serological markers of liver cancer. Best Pract Res Clin Gastroenterol 19(1):91–99. ISSN 1521-6918 (Print) 1521-6918

    Article  CAS  Google Scholar 

  • Zeng J et al (2014) Metabolomics study of hepatocellular carcinoma: discovery and validation of serum potential biomarkers by using capillary electrophoresis-mass spectrometry. J Proteome Res 13(7):3420–3431. ISSN 1535-3907 (Electronic) 1535-3893 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/24853826

    Article  CAS  Google Scholar 

  • Zhan P, Qian Q, Yu LK (2013) Serum VEGF level is associated with the outcome of patients with hepatocellular carcinoma: a meta-analysis. Hepatobiliary Surg Nutr 2(4):209–215. ISSN 2304-3881 (Print) 2304-3881

    Google Scholar 

  • Zhang Y et al (2012) Circulating tumor cells in hepatocellular carcinoma: detection techniques, clinical implications, and future perspectives. Semin Oncol 39(4):449–460. ISSN 0093-7754. Available at: https://www.sciencedirect.com/science/article/pii/S0093775412001157

    Article  CAS  Google Scholar 

  • Zhang Y et al (2016) Microfluidic chip for isolation of viable circulating tumor cells of hepatocellular carcinoma for their culture and drug sensitivity assay. Cancer Biol Ther 17(11):1177–1187. ISSN 1538-4047

    Article  CAS  Google Scholar 

  • Zhao Y et al (2015) Significance of combined tests of serum golgi glycoprotein 73 and other biomarkers in diagnosis of small primary hepatocellular carcinoma. Cancer Biomark 15(5):677–683. ISSN 1574-0153

    Article  CAS  Google Scholar 

  • Zhong S et al (2002) Silencing of GSTP1 gene by CpG island DNA hypermethylation in HBV-associated hepatocellular carcinomas. Clin Cancer Res 8(4):1087–1092. ISSN 1078-0432 (Print) 1078-0432 (Linking). Available at: http://www.ncbi.nlm.nih.gov/pubmed/11948118

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Biochemistry Department, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt

    Nabil Mohie Abdel-Hamid & Shimaa Ali Abass

Authors
  1. Nabil Mohie Abdel-Hamid
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shimaa Ali Abass
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nabil Mohie Abdel-Hamid .

Editor information

Editors and Affiliations

  1. Division of Clinical Immunology, Karolinska University Hospital, Huddinge, Sweden

    Nima Rezaei

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Abdel-Hamid, N.M., Abass, S.A. (2023). Perspectives in Biochemical Staging of Hepatocellular Carcinoma Over the Current Microscopical Methodology. In: Rezaei, N. (eds) Handbook of Cancer and Immunology. Springer, Cham. https://doi.org/10.1007/978-3-030-80962-1_148-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-80962-1_148-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-80962-1

  • Online ISBN: 978-3-030-80962-1

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation