Multifocal hepatocellular carcinoma: intrahepatic metastasis or multicentric carcinogenesis?

Multifocal hepatocellular carcinoma (HCC) may be multiple HCCs of multicentric origin (MO) or intrahepatic metastases (IM) arising from a primary HCC. Numerous attempts to differentiate the two types of multifocal HCC have been made including the valuation of the clinicopathologic characteristics of MO and IM patients and the recurrence time, loss-of-heterozygosity analysis of specific DNA microsatellite loci to distinguish multiclonal MO from IM of monoclonal origin, and the research of diagnostic and progression markers through genomic and proteomic analyses. These approaches, however, have been unsatisfactory hitherto. Recently, a multi-omic analysis of HBV-related multifocal HCCs, including intergraded genomics and transcriptomics, was performed and the results, validated by a cohort of 174 HCC patients, were correlated with HCC clinicopathological data. The two multifocal HCC types were effectively discerned by multi-omics profiling that could predict HCC clonality and aggressiveness. Further, the dual-specificity protein kinase TTK was recognized as a prognostic marker for HCC. Multi-omics strategy potentially opens new perspectives for the diagnosis, prognosis and personalized treatment of multi-focal HCC. Further work aimed at extending this strategy to HCC with other etiology, simplifying the analysis, and reducing its costs is necessary for its routine clinical application.