Recent advances in molecular biomarkers for patients with hepatocellular carcinoma

ABSTRACT

Introduction: Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide and recurrence rate after curative resection remains high. To improve HCC prognosis, novel sensitive biomarkers and targeted molecular therapies are needed. Accumulation of multiple genetic aberrations caused by pathologically derived liver damage results in HCC carcinogenesis. Elucidating the genes associated with tumorigenesis and progression of HCC may lead to the development of early detection and prognosis markers and to the identification of therapeutic targets.

Areas covered: We review recently reported (January 2017-March 2019) HCC-associated molecules, including protein-coding genes, microRNAs, long non-coding RNAs, and methylated gene promoters.

Expert opinion: The molecules reviewed have the potential to be clinical biomarkers and therapeutic targets for HCC. The accumulation and understanding of genetic and epigenetic data are essential to improve the management of HCC patients.

KEYWORDS:

• Biomarker
• DNA methylation
• hepatocellular carcinoma
• long noncoding RNA
• microRNA

Article Highlights

• Despite the development of various therapeutic modalities, the prognosis of HCC patients is still dismal. Sensitive biomarkers for early detection and prognosis, and treatment response prediction are needed to improve outcomes of patients with HCC.

• We reviewed recent literatures (from January 2017 to May 2019) on molecular biomarkers related to the initiation and progression of HCC, which can be potential diagnostic tools and therapeutic targets.

• Various oncogenes and tumor suppressor genes were reported recently. MCM6, KIFC1, CAB39, LOXL2 and CXCR4 as representative examples of oncogenes and RFX1, TLN1, GPR155 and IFIT as tumor suppressor genes were highlighted in this review article.

• Aberrant DNA methylation was detected as an epigenetic alteration which is associated with pathogenesis of HCC and, therefore, SALL4, CTCFL, SHC3 were introduced as methylated genes.

• Non-cording RNAs are also associated with the initiation and progression of HCC. Several micro RNAs (MIR665, MIR425, and MIR122) and long non-coding RNAs (UBE2CP3, P7, and LNCARSR) were introduced.

• Further research is required to bring promising candidate molecules into clinical use, however, the accumulation of genetic and epigenetic data is an essential step for future improvement of management of patients with HCC.

• HCC treatment is about to enter an era of personalized medicine based on a genetic profiling which will enable treatments to be selected that are based on accurate prediction of prognosis and treatment sensitivity.

Acknowledgments

We thank Jeremy Allen, PhD, from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.