lncRNA signature with prognostic relevance in stage I EOC

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 hsa-miR-200c-3p can predict patients' outcome. In the present study, we analyzed the expression of long non-coding RNAs (lncRNAs) 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 are 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 hsa-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 3.81-63.36 CI 95%). Conclusions: We have identified a non-coding transcriptional signature predictor of survival and biomarker of relapse for stage I EOC.

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