Journal Article

Comprehensive analysis of five long noncoding RNAs expression as competing endogenous RNAs in regulating hepatoma carcinoma

Li, Jun, Wei, Ya‐Qing, Lou, Xin, Feng, Shuang, Yu, Dong, Sun, Jin‐Jin

2019

Overview

Liver cancer is the most common cancer and is the epitome of a recalcitrant cancer. Increasing evidence shown that long noncoding RNAs (lncRNA) were associated with cancer‐related death and could function as a competing endogenous RNA (ceRNA). To explore regulatory roles and potential prognostic biomarkers of lncRNA for liver cancer, RNA‐sequencing expression data were downloaded from the TCGA database and GEO database. A total of 357 patients were randomly divided into a discovery group and a validation group, of which 313 patients can obtain clinical data. In discovery phrase, 58 lncRNAs, 16 miRNAs, and 34 mRNAs were screened to construct the ceRNA network based on 252 patients employed from discovery group. Univariate and multivariate Cox hazard regression analysis model revealed that five lncRNAs (AATK‐AS1, C10orf91, LINC00162, LINC00200, and LINC00501) from 58 lncRNAs were formulated to predict the overall survival (OS). We used the value of gene expression and regression coefficients to construct a risk score based on the five lncRNAs. Next, we validated our model in the GSE116174 dataset (n = 64) and the validation group (n = 94) from TCGA database. Subgroup analysis suggest that the five lncRNAs played critical parts in early stage in cancer from both discovery and validation groups. The five lncRNAs were also found to be associated with immune cells infiltration including CD4+ memory activated, NK cells activated and mast cells activated, then the results were also validated according to the validation group. Furthermore, KEGG pathway enrichment analysis showed that these nine coexpressed modules using the method of WGCNA, and many of these pathways are associated with the development and progression of disease. At last, the transcription factor binding sites (TFBS) of the five lncRNAs were predicted, which help us to understand the potential mechanism that the TFBS adjusted the ceRNA network. In summary, the ceRNA regulatory network may contribute to a better understanding of liver cancer mechanism and provide potential prognostic biomarkers and therapeutic targets. lncRNA play critical roles in the development of cancer and may have close relation to prognosis. we constructed a ceRNA network, and a risk‐score model based on eight‐lncRNA to predicted the OS time of HCC patients.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Binding Sites / Biomarkers / Biomarkers, Tumor - genetics / Cancer Biology / Carcinoma, Hepatocellular - genetics / CD4 antigen / Cell cycle / ceRNA / Data processing / FDA approval / Female / Gene expression / Gene Expression Profiling - methods / Gene Expression Regulation, Neoplastic / Gene Regulatory Networks / Hepatoma / hepatoma carcinoma / Humans / Immunological memory / Kinases / Liver cancer / Liver Neoplasms - genetics / lncRNA / Male / Mast cells / Medical prognosis / MicroRNAs - genetics / Original Research / Patients / Prognosis / Ribonucleic acid / Risk assessment / RNA / RNA, Long Noncoding - chemistry / RNA, Long Noncoding - genetics / Roles / Sequence Analysis, RNA / Studies / Survival Analysis / TCGA / Therapeutic applications