Development of genomic instability-associated long non-coding RNA signature: a prognostic risk model of clear cell renal cell carcinoma

Abstract

Background: Renal cell carcinoma is one of the most common cancers in the urinary system. Renal clear cell carcinoma is the most lethal of all pathological subtypes. Genomic instability was recently reported to be relative with occurrence and development of renal cells. The biological roles of long non-coding RNAs (lncRNAs) in tumorigenesis have been increasingly valued, and various lncRNAs were found to be oncogenes or cancer suppressors. Here, we identified a novel genomic instability-associated lncRNAs (GILncs) model for ccRCC patients to predict overall survival (OS).Methods: The Cancer Genome Atlas database was applied to obtain full transcriptome data, somatic mutation profiles and clinical characteristics. The differential expressed lncRNAs between genome-unstable (GU) like group and genome-stable (GS) like group were defined as GILncs, with |logFC| >1 and adjusted p value< 0.05 of false discovery rate. All samples were allocated into GU-like type and GS-like type based on expression of GILncs using hierarchical cluster analyses. A genomic instability-associated lncRNA signature (GILncSig) was constructed using parameters of included lncRNAs. Quantitative real-time PCR analysis was used to detect the expression of included lncRNAs in vitro. Validation of the risk model was performed by Kaplan–Meier (K-M) log-rank test, Time-dependent receiver operating characteristic curve analysis and multivariate Cox regression analysis.Results: 46 lncRNAs were identified as GILncs. LINC00460, AL139351.1 and AC156455.1 were employed for GILncSig calculation based on the results of multivariate Cox analysis. GILncSig was confirmed as an independent index for predicting OS and concerned with malignant progression of ccRCC. Additionally, the GILncSig Score presented better efficiency and accuracy than two lncRNA-related models published before.Conclusion: GILncSig Score was qualified as a critical indicator independent from other clinical factors for predicting prognostic risk of ccRCC patients.