Liver-enriched Genes are Associated with the Prognosis of Patients with Hepatocellular Carcinoma

Abstract

Tissue-enriched genes are highly expressed in one particular tissue type and represent distinct physiological processes. The dynamic profile of tissue-enriched genes during tumorigenesis and progression remains largely unstudied. Here, we identified tissue-enriched genes from 12 tissue types based on RNA sequencing data from the Cancer Genome Atlas (TCGA), and found that the liver had the largest number of such genes among the 12 tissue types. The characteristics of liver-enriched genes were further investigated. Most liver-enriched genes were downregulated and metabolism-related genes, which were associated with pathological stage and dedifferentiation in patients with hepatocellular carcinoma (HCC). Hypermethylation might be a mechanism underlying the downregulation of liver-enriched genes. We constructed a liver-enriched gene set and demonstrated that it is associated with the prognosis of the patients with HCC both in the TCGA cohort and the Gene Expression Omnibus (GEO) datasets. Moreover, we discovered that the degree of the dissimilarity between tumors and normal tissues was correlated with the prognosis of patients with HCC and the biological behaviours of the tumors. These results will help identify prognostic biomarkers of patients with HCC, and enhance our understanding of the molecular mechanisms of hepatocarcinogenesis and progression.