Comprehensive pathway-related genes signature for prognosis and recurrence of ovarian cancer

Abstract

Background Ovarian cancer (OC) is a highly malignant disease with a poor prognosis and high recurrence rate. At present, there is no accurate strategy to predict the prognosis and recurrence of OC. The aim of this study was to identify gene-based signatures to predict OC prognosis and recurrence. Methods mRNA expression profiles and corresponding clinical information regarding OC were collected from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) and LASSO analysis were performed, and Kaplan–Meier curves, time-dependent ROC curves, and nomograms were constructed using R software and GraphPad Prism7. Results We first identified several key signalling pathways that affected ovarian tumorigenesis by GSEA. We then established a nine-gene-based signature for overall survival (OS) and a five-gene-based-signature for relapse-free survival (RFS) using LASSO Cox regression analysis of the TCGA dataset and validated the prognostic value of these signatures in independent GEO datasets. We also confirmed that these signatures were independent risk factors for OS and RFS by multivariate Cox analysis. Time-dependent ROC analysis showed that the AUC values for OS and RFS were 0.640, 0.663, 0.758, and 0.891, and 0.638, 0.722, 0.813, and 0.972 at 1, 3, 5, and 10 years, respectively. The results of the nomogram analysis demonstrated that combining two signatures with the TNM staging system and tumour status yielded better predictive ability. Conclusion In conclusion, the two-gene-based signatures established in this study may serve as novel and independent prognostic indicators for OS and RFS.