Bioinformatical identification of key genes regulated by IGF2BP2-mediated RNA N6-methyladenosine and prediction of prognosis in hepatocellular carcinoma.

Abstract

The treatment of hepatocellular carcinoma (HCC), a malignant cancer with global spread, remains unsatisfactory, and novel prognostic biomarkers need to be identified. N6-methyladenosine (m6A) has been found to regulate tumor initiation and progression through different mechanisms. As a dynamic and reversible messenger RNA (mRNA) modification, m6A can be read by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). IGF2BP2 targets thousands of mRNA transcripts, which may be involved in HCC progression. In this study, we integrated 4 classes of datasets including The Cancer Genome Atlas (TCGA)-LICH, m6A-sequencing data of HepG2 cells, and RNA-sequencing data of IGF2BP2-knockdown HepG2 cells to explore the key genes regulated by IGF2BP2-mediated m6A in HCC. The expression and m6A modification of candidates were validation in independent microarray expression profile of HCC tissue and annotated m6A database RMBase. The relationship of immune cell infiltration and the genes expression was estimated by CIBERSORT and TIMER. A total of 89 candidate genes were filtered. Next, cluster analysis was performed base on functions and pathways to identify the enrichment pathways. By constructing a protein-protein interaction (PPI) network, we found 54 nodes. Ten significant genes were filtered from the PPI. These genes were validated in data of an independent microarray and an m6A database. We found that the upregulation of these 10 genes was associated with poor prognosis. In addition, we showed the expression of these 10 genes was associated with the infiltration of variety of immune cell and tumor purity. These identified genes may provide novel insights and facilitate the development of potential biomarkers for HCC diagnosis, as well as provide clues for IGF2BP2 inhibition therapy in HCC.