Gene signatures in the management of hepatocellular carcinoma

Clinical management of hepatocellular carcinoma (HCC) is a complex process. Currently existing prognostic staging systems have substantially improved the clinical outcome of patients by guiding treatment decision and allocation of medical resources. However, there is still room to refine many aspects of the framework based on more precise clinical outcome prediction and understanding of HCC molecular pathogenesis. Recent development of genomic technologies has enabled survey of molecular aberrations and deregulations directly from patient specimens in a comprehensive manner. This also has provided clues to therapeutic/preventive targets that could also serve as prognostic/predictive biomarkers. Structural alterations and chemical modifications of genomic DNA have been shown to be useful to guide molecular targeted therapies in some cancers. Gene expression signatures also hold promise as a way to probe functional biological status of the tumor specimen. However, accumulated studies have revealed roadblocks toward the goal to utilize the information in clinic. In this review, we discuss the gene signature's potential application, its pros and cons as a clinical test, technical issues in assay development, and strategies for clinical deployment in the context of HCC management. Recent updates of HCC gene signatures as well as emerging alternative modalities are also overviewed.