Comparative analysis of molecular aberration in different genders for identification of key pathways in hepatocellular carcinoma.

e23192 Background: The incidence rate of hepatocellular carcinoma (HCC) varies significantly between genders, being higher in men than in women. While the molecular mechanisms remain unexplored, we systematically analyzed the gene expression and SNV signature to identify key molecular aberrations and pathways. Methods: Gene expression and simple nucleotide variation data of 407 HCC patients with HCC including 140 females and 267 males were collected. We identified genes with differential mutation frequency in two cohorts using Fisher’s exact test (p-value < 0.05), and Deseq2 to identify differential expression genes (FDR < 0.05 and fold change > 2). Enrichment analysis was applied using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Reactome database (p adjust < 0.05). Results: In total, 103 genes with differential mutation frequency in two cohorts were identified. Of these genes, 57 genes were differentially expressed, and the number of up-regulated genes in males and females were 21 and 36, respectively. The genes that show significant up-regulation in males are KDM5D and ANKFN1 which have the log2(fold change) of 7.49 and 4.45. The genes that show significant up-regulation in females are SYT13 and SCD5 which have the log2(fold change) of 2.33 and 2.29. The result of enrichment analysis showed that the up-regulated genes in males and females were involved in different biological pathways. In males, the up-regulated genes mainly participated in the PPAR signaling pathway. In females, the up-regulated genes mainly participated in the Rho GTPase cycle, regulation of insulin secretion and integration of energy metabolism. Conclusions: In this study, 57 genes with differential mutation frequency and differential expression between males and females with HCC were identified based on TCGA dataset. Enrichment analysis result indicated that these genes are mainly involved in signaling pathways relevant to carcinogenesis and metabolism.