Development of a Genomic Instability-Derived lncRNAs-Based Risk Signature as a Predictor of Prognosis for Endometrial Cancer.

Abstract

Endometrial cancer (EC) ranks fourth in the incidence rate among the most frequent gynaecological malignancies reported in the developed countries. Approximately 280,000 endometrial cancer cases are reported worldwide every year. Genomic instability and mutation are some of the favourable characteristics of human malignancies such as endometrial cancer. Studies have established that the majority of genomic mutations in human malignancies are found in the chromosomal regions that do not code for proteins. In addition, the majority of transcriptional products of these mutations are long non-coding RNAs (lncRNAs). In this study, 78 lncRNA genes were found on the basis of their mutation counts. Then, these lncRNAs were investigated to determine their relationship with genomic instability through hierarchical cluster analysis, mutation analysis, and differential analysis of driving genes responsible for genomic instability. The prognostic value of these lncRNAs was also assessed in patients with EC, and a risk factor score formula composed of 15 lncRNAs was constructed. We then identified this formula as genome instability-derived lncRNA-based gene signature (GILncSig), which stratified patients into high- and low-risk groups with significantly different outcome. And GILncSig was further validated in multiple independent patient cohorts as a prognostic factor of other clinicopathological features, such as stage, grade, overall survival rate. We observed that a high-risk score is often associated with an unfavourable prognosis in patients with EC.