TP53 Mutation Related and Directly Regulated lncRNA Prognosis Markers in Hepatocellular Carcinoma

Abstract

Xiulei Zhang,1 Zhihao Fu,2 Xiao Zhang2 1Department of Microbiome Laboratory, Henan Provincial People’s Hospital, Zhengzhou University, Zhengzhou, 450003, People’s Republic of China; 2Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, Zhengzhou University, Zhengzhou, 450003, People’s Republic of ChinaCorrespondence: Xiulei Zhang; Xiao Zhang Email [email protected]; [email protected]: TP53 mutation is the most common genetic variation type in Hepatocellular carcinoma (HCC). We aim to illustrate the landscape of genomic alterations and TP53 mutation related and directly regulated lncRNA prognosis markers.Materials and Methods: Utilizing the clinical and transcriptome data from The Cancer Genome Atlas (TCGA) website, we present the landscape of genomic alterations and RNA differential expression profiles. By analyzing the ENCODE TP53 ChIP-seq data, we get the TP53 chromatin binding profiles. By Kaplan–Meier (KM) survival analysis and ROC analysis, we identify lncRNA prognosis markers.Results: TP53 ranks the highest mutation frequency gene and the maximum mutation type of TP53 is Missense Mutation (> 2.5× 104). TP53 mutation showed poor clinical outcome among the pathological Stage II and Stage III HCC patients. By differential expression analysis of the TP53 wild type and mutation HCC, we find thousands of misregulated genes, including 699 differential expression lncRNAs (p < 0.05, |log2FC| ≥ 1). Functional enrichment analysis of the misregulated genes shows that TP53 mutation events mainly alter DNA replication, cell cycle and immune response signaling pathways. By estimation of tumor-infiltrating immune cells through CIBERSORT, we find that the TP53 mutation events are significantly correlated with the different proportions of nine immune cells. We then integratively analyze the differential expression lncRNAs in TP53 wild type and mutation groups and the TP53 ChIP-seq binding lncRNAs, and get 112 overlap lncRNAs. By Kaplan–Meier survival analysis and ROC analysis, we identify two lncRNAs (RP4-736L20.3 and SNRK-AS1) that show significant prognosis value. Using the collected HCC samples, we validate the misregulated expression of RP4-736L20.3 and SNRK-AS1.Conclusion: The work presents the landscape of genomic variations and two TP53 mutation related and directly regulated lncRNA prognosis markers of HCC.Keywords: hepatocellular carcinoma, genomic variations, TP53 mutation, lncRNA, prognosis marker, HCC

Keywords

• hepatocellular carcinoma
• genomic variations
• tp53 mutation
• lncrna
• prognosis marker