LncRNAs as novel indicators of patients' prognosis in stage i epithelial ovarian cancer: A retrospective and multicentric study

Purpose: Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs and is characterized by good prognosis with fewer than 20% of patients relapsing. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. We have demonstrated that in stage I EOC miR-200c-3p can predict patients' outcome. In the present study, we analyzed the expression of long non-coding RNAs (lncRNA) to enable potential definition of a non-coding transcriptional signature with prognostic relevance for stage I EOC. Experimental Design: 202 snap-frozen stage I EOC tumor biopsies, 47 of which relapsed, were gathered together from three independent tumor tissue collections and subdivided into a training set (n = 73) and a validation set (n = 129). Median follow up was 9 years. LncRNAs' expression profiles were correlated in univariate and multivariate analysis with overall survival (OS) and progression-free survival (PFS). Results: The expression of lnc-SERTAD2-3, lnc-SOX4-1, lnc- HRCT1-1, and PVT1 was associated in univariate and multivariate analyses with relapse and poor outcome in both training and validation sets (P < 0.001). Using the expression profiles of PVT1, lnc-SERTAD2-3, and miR-200c-3p simultaneously, it was possible to stratify patients into high and low risk. The OS for high- and low-risk individuals are 36 and 123 months, respectively (OR, 15.55; 95% confidence interval, 3.81-63.36). Conclusions: We have identified a non-coding transcriptional signature predictor of survival and biomarker of relapse for stage I EOC. Clin Cancer Res; 23(9); 2356-66.