Abstract
Long non-coding RNAs (lncRNAs) have been considered as biomarkers for the carcinogenesis and development of various cancers. However, the prognostic significance of lncRNAs in renal cell carcinoma (RCC) remains unclear. This study aimed to determine the predictive ability of lncRNAs in clear cell RCC (ccRCC). Among the cohort of kidney renal clear cell carcinoma (KIRC) of the The Cancer Genome Atlas (TCGA), 525 patients were enrolled in our study. Expression of lncRNAs based on RNAseq was obtained from TCGA. Kaplan-Meier prognostic analysis and a Cox proportional hazards regression model were used to assess related factors. The lncRNA signature was then validated in an independent cohort of an additional 60 ccRCC patients. Hierarchical clustering of the KIRC TCGA dataset identified 26 differentially expressed lncRNAs (11 down-regulated and 15 up-regulated) using average linkage clustering. Kaplan-Meier survival analysis identified 30 statistically significant lncRNAs that strongly predicted prognosis, with 4 ccRCC-specific lncRNAs (TCL6, PVT1, MIR155HG, and HAR1B) being differentially expressed and correlating significantly with OS. Patients assigned to the high-risk group were associated with poor OS compared with patients in the low-risk group (HR = 2.57; 95%CI, 1.89-3.50; p < 0.001). This finding was validated in the Tongji Hospital cohort, and the four-lncRNA signature was shown to be significantly predictive of ccRCC prognosis (p < 0.001). In this study, we constructed an applicable four-lncRNA-based classifier as a reliable prognostic and predictive tool for OS in patients with ccRCC.