Molecular subtyping of hepatocellular carcinoma: A step toward precision medicine

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent and fatal digestive tumors. Treatment for this disease has been constraint by heterogeneity of this group of tumors, which has greatly limited the progress in personalized therapy. Although existing studies have revealed the genetic and epigenetic blueprints that drive HCCs, many of the molecular mechanisms that lead to HCCs remain elusive. Recent advances in techniques for studying functional genomics, such as genome sequencing and transcriptomic analyses, have led to the discovery of molecular mechanisms that participate in the initiation and evolution of HCC. Integrative multi‐omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical outcomes. Deciphering similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized therapeutics. This review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.

A Five-Gene-Based Prognostic Signature for Hepatocellular Carcinoma

“…The first-line agents for treatment of advanced HCC include sorafenib, combined use of atezolizumab and bevacizumab, and lenvatinib, and adoptive cell transfer therapy, oncolytic viruses, in addition to locoregional therapies also have a potential benefit (3). Of note, the efficacy of optimal treatment for HCC has been limited by heterogeneity of this malignancy, which has constrained the advancement in personalized therapy (4). Cell division cycle 20 (CDC20), in combination with G2 and S-phase expressed 1 (GTSE1), proliferating cell nuclear antigen (PCNA), and minichromosome maintenance complex component 6 (MCM6), could have effects on cell cycle of HCC, while serving as markers for poor prognosis (5).…”

“…The first-line agents for treatment of advanced HCC include sorafenib, combined use of atezolizumab and bevacizumab, and lenvatinib, and adoptive cell transfer therapy, oncolytic viruses, in addition to locoregional therapies also have a potential benefit ( 3 ). Of note, the efficacy of optimal treatment for HCC has been limited by heterogeneity of this malignancy, which has constrained the advancement in personalized therapy ( 4 ).…”

Patients with polyclonal hepatocellular carcinoma are at a high risk of early recurrence and have a poor recurrence-free survival period

“…In this study, we evaluated the CC number, a surrogate marker of intratumor heterogeneity, to investigate its clinical relevance in HCC. In general, HCC is reported to be highly heterogeneous [2][3][4]. In our sample set, the rate of homogeneous tumors with a CC number of 0 and the rate of heterogeneous tumors with a CC number of greater than 1 were 23.5% and 76.5%, respectively, suggesting that HCC was often a heterogeneous tumor in our cohort.…”

“…Although surgical resection improves the survival of HCC patients, early recurrence after hepatic resection is a poor prognostic factor for patients with HCC. HCC is a highly heterogeneous cancer [2][3][4]. Molecular heterogeneity and a lack of biomarkers for recurrence have contributed to the poor prognosis of HCC patients.…”

Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

“…With the progress in next-generation sequencing (NGS) and the development of multi-omics technologies, individual variability in gene expression patterns can be assessed (10). This is especially important in the case of HCC, cancer with a high degree of intra-and inter-tumoral heterogeneity and a variety of molecular subtypes (11)(12)(13). Multi-omics-based biomarker screening has a great potential in enabling personalized treatment or risk-stratified management of HCC patients (14)(15)(16).…”