A long non-coding RNA signature to improve prognostic prediction in clear cell renal cell carcinoma

Accumulating research reports have indicated that long non-coding RNAs (lncRNAs) are abnormally expressed in many types of cancers. However, few lncRNA signatures for predicting cancer prognosis have been established. Our goal is to establish a lncRNA signature for predicting the prognosis of clear cell renal cell carcinoma (ccRCC).

We downloaded KIRC lncRNA FPKM (Fragments Per Kilobase of transcript per Million Fragments) standardized expression data from The Cancer Genome Atlas (TCGA) by using the TANRIC tool. We established an 11-lncRNA signature that was clearly linked to the overall survival (OS) rates in the training and test sets.

The training set was divided into the high-risk and low-risk subgroups, between which the OS was disparate (HR = 1.51, 95%CI = 1.39-1.64, P < 0.0001). The accuracy of the 11-lncRNA signature for predicting prognosis was confirmed in the test set. Further analysis revealed that the prognostic value of this signature was independent of the neoplasm grade and TNM stage. Gene set enrichment analysis (GSEA) was performed, and a summary of 4 gene sets related to canonical pathway, biological process, molecular function and cellular component was obtained. We demonstrated the biological function of these lncRNAs in ccRCC cell lines and found that LINC00488 and HOTTIP promoted tumour proliferation and inhibited apoptosis. However, LINC-PINT had the opposite effect.

The establishment of the 11-lncRNA signature indicated the underlying biochemical functional roles of the selected lncRNAs in ccRCC. Our results may provide a reliable theoretical basis for clinical evaluation of ccRCC prognosis.