A Platinum Resistance-Related lncRNA Signature for Risk Classification and Prognosis Prediction in Patients with Serous Ovarian Cancer

Abstract

Accurate risk stratification for patients with serous ovarian cancer (SOC) is pivotal for treatment decisions. In this study, we identified a lncRNA-based signature for predicting platinum resistance and prognosis stratification for SOC patients. We analyzed the RNA-sequencing data and the relevant clinical information of 295 SOC samples obtained from The Cancer Genome Atlas (TCGA) database and 180 normal ovarian tissues from the Genotype-Tissue Expression (GTEx) database. A total of 284 differentially expressed lncRNAs were screened out between platinum-sensitive and platinum-resistant groups by univariate Cox regression analysis. Then, a signature consisting of eight prognostic lncRNAs was used to construct a lncRNA score model by least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The ROC analysis showed that this signature had a good predictive performance for chemotherapy response in the training set (AUC = 0.8524) and the testing and whole sets with 0.8142 and 0.8393 of AUC, respectively. Dichotomized by the risk score of lncRNAs (lncScore), the high-risk patients showed significantly shorter progression-free survival (PFS) and overall survival (OS). Based on the final Cox model, a nomogram comprising the 8-lncRNA signature and 3 clinicopathological risk factors was then established for clinical application to predict the 1, 2, and 3-year PFS of SOC patients. The gene set enrichment analysis (GSEA) revealed that genes in the high-risk group were active in ATP synthesis, coupled electron transport, and mitochondrial respiratory chain complex assembly. Overall, our findings demonstrated the potential clinical significance of the 8-lncRNA-based classifier as a novel biomarker for outcome prediction and therapy decisions in SOC patients with platinum treatment.