Biomarkers: What Role Do They Play (If Any) for Diagnosis, Prognosis and Tumor Response Prediction for Hepatocellular Carcinoma?
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Hepatocellular carcinoma (HCC) is a common illness that affects patients worldwide. The disease remains poorly understood though several recent advances have increased the understanding of HCC biology and treatment.
A literature review was conducted to understand the role of biomarkers in HCC clinical practice and highlight areas of critical investigation.
Candidate biomarkers may include differential alterations in HCC genomics, epigenomics, gene expression and transcriptomic profiles, protein expression, cellular composition of the microenvironment, and vasculature. To date no circulating or tumor diagnostic markers have been established in this disease. Likewise, prognostication is currently adjudicated by clinicopathologic features and it remains unclear if the incorporation of any biomarkers may help enhance the prognostic understanding following curative intents like surgery, transplant, and select regional therapy or palliative treatment including embolization or systemic therapy. Predictive biomarkers are investigational and are under evaluation for molecular pathways like TOR, MET, VEGFA, and FGF19. Tumoral genomics, HLA allele diversity and tumoral immune activation as predictive markers for immune checkpoint inhibitors are key focuses of ongoing research.
Diagnostic, prognostic, and predictive tumor and circulating biomarkers for HCC have not been defined though several markers have been proposed to guide patient care.
KeywordsHepatocellular carcinoma Biomarkers Diagnostic Predictive Prognostic
Compliance with ethical standards
Conflict of interest
JJH reports consultation fees from Bristol Myers Squibb, Eli Lilly, Eisai, and CtyomX and research funds from Bristol Myers Squibb. GKA reports research support from ActaBiologica, Agios, Array, Astra Zeneca, Bayer, Beigene, BMS, Casi, Celgene, Exelixis, Genentech, Halozyme, Incyte, Lilly, Mabvax, Novartis, OncoQuest, Polaris Puma, QED, Roche; and consulting fees from 3DMedcare, Agios, Alignmed, Amgen, Antengene, Aptus, Aslan, Astellas, Astra Zeneca, Bayer, Beigene, Bioline, BMS, Boston Scientifc, Bridgebio, Carsgen, Celgene, Casi, Cipla, CytomX, Daiichi, Debio, Delcath, Eisai, Exelixis, Genoscience, Gilead, Halozyme, Hengrui, Incyte, Inovio, Ipsen, Jazz, Jansen, Kyowa Kirin, LAM, Lilly, Loxo, Merck, Mina, Newlink Genetcis, Novella, Onxeo, PCI Biotech, Pfizer, Pharmacyte, Pharmacyclics, Pieris, QED, Redhill, Sanofi, Servier, Silenseed, Sillajen, Sobi, Targovax, Tekmira, Twoxar, Vicus, Yakult, and Yiviva.
- 2.GK A-A, WJ, M L, et al. Liver and Bile Duct Cancer. 6th ed: Philadelphia, 2018.Google Scholar
- 5.Vilgrain V, Pereira H, Assenat E, et al. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017;18:1624–1636.CrossRefGoogle Scholar
- 13.Zhu AX, Kang Y-K, Yen C-J, et al. REACH-2: a randomized, double-blind, placebo-controlled phase 3 study of ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated baseline alpha-fetoprotein (AFP) following first-line sorafenib. J Clin Oncol. 2018;36:4003.CrossRefGoogle Scholar
- 37.El-Assal ON, Yamanoi A, Soda Y, et al. Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver. Hepatology. 1998;27:1554–1562.CrossRefGoogle Scholar
- 38.van der Pol CB, Lim CS, Sirlin CB, et al. Accuracy of the liver imaging reporting and data system in computed tomography and magnetic resonance image analysis of hepatocellular carcinoma or overall malignancy—a systematic review. Gastroenterology. 2018. https://doi.org/10.1053/j.gastro.2018.11.020.Google Scholar
- 42.Soresi M, Magliarisi C, Campagna P, et al. Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res. 2003;23:1747–1753.Google Scholar
- 56.Zhou ZQ, Tong DN, Guan J, et al. Follicular helper T cell exhaustion induced by PD-L1 expression in hepatocellular carcinoma results in impaired cytokine expression and B cell help, and is associated with advanced tumor stages. Am J Transl Res. 2016;8:2926–2936.Google Scholar