lncRNAs as Novel Indicators of Patients' Prognosis in Stage I Epithelial Ovarian Cancer: A Retrospective and Multicentric Study

Abstract

<b>Purpose:</b> 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 <i>miR-200c-3p</i> 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.<b>Experimental Design:</b> 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 (<i>n</i> = 73) and a validation set (<i>n</i> = 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).<b>Results:</b> The expression of <i>lnc-SERTAD2</i>-<i>3, lnc-SOX4-1, lnc-HRCT1-1</i>, and <i>PVT1</i> was associated in univariate and multivariate analyses with relapse and poor outcome in both training and validation sets (<i>P</i> < 0.001). Using the expression profiles of <i>PVT1, lnc-SERTAD2</i>-<i>3</i>, and <i>miR-200c-3p</i> 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).<b>Conclusions:</b> We have identified a non-coding transcriptional signature predictor of survival and biomarker of relapse for stage I EOC. <i>Clin Cancer Res; 23(9); 2356-66. ©2016 AACR</i>.