Transcriptome changes in Mcl-1-null livers as mechanistic basis and prognostic biomarkers for hepatocellular carcinoma

Aged hepatocyte specific-Mcl-1 knockout (MKO-hep) mice develop liver tumors mimicking human hepatocellular carcinoma (HCC), thus serving as a viable model for exploring prognostic and prophylactic biomarkers of HCC. However, despite the phenotypic resemblance, the molecular pathways that may contribute to the tumorigenesis of MKO-hep livers remain elusive. This study employed deep RNA-sequencing to profile poly(A)+ transcriptomes in the livers from two sources of MKO-hep mice, and 518 transcripts were found to be differentially expressed (DETs) between control and MKO-hep livers. Further analysis revealed preponderance of altered genes in canonical pathways related to DNA integrity and tissue inflammation. Interestingly, clinical correlation showed that 56 human homologs of these DETs are associated with patient survival, thus uncovering potential prognostic biomarkers for HCC.