**9. Future directions**

Elucidating the molecular pathogenesis of HCC on human samples has been an onerous task due to certain limitations such as varying etiologies among studied patients, changes likely to arise during the different stages of the disease or progression of HCC, and heterogeneity of the disease. Moreover, the success of studies is hampered by the fact that hepatic transcriptome is among the most complex of any organ, and the study of tumor formation in liver can be thorny and complicated by the continuous change of the transcriptome during liver regeneration after hepatectomy. Besides, cancer progresses through a series of histopathological stages during which genetic alterations accumulate and, in consequence, the pattern of genetic expression changes complicates the interpretation of the genetic changes in human HCC. These limitations have hampered development of proper therapeutics that was further complicated by recurrences even after aggressive local therapies.

The advances in high-throughput "omics" and next-generation sequencing technologies have been providing unprecedented biological insights related to pathogenesis of HCC. Undoubtedly, comparative and integrative genomics approaches are promising to lead to novel and robust biomarkers for improved diagnosis, prognosis, and treatment of HCC. The systems approach via the integration of data reflecting alterations at genomic, transcriptomic, proteomic, and epigenomics levels will ultimately converge toward a personalized medicine that will improve diagnosis, treatment and prevention of liver cancer.
