Abstract

BackgroundEndometrial cancer (UCEC) is a complex malignant tumor characterized by both genetic level and clinical trial. Patients with UCEC exhibit the similar clinical features, however, they have distinct outcomes due to molecular heterogeneity. The aim of this study was to access the prognostic value of long non-coding RNAs (lncRNAs) in UCEC patients and to identify potential lncRNA signature for predicting patients’ survival and improving patient-tailored treatment.MethodsWe performed a comprehensive genome-wide analysis of lncRNA expression profiles and clinical data in a large cohort of 301 UCEC patients. UCEC patients were randomly divided into the discovery cohort (n = 150) and validation cohort (n = 151). A novel lncRNA-focus expression signature was identified in the discovery cohort, and independently accessed in the validation cohort. Additionally, the lncRNA signature was evaluated by multivariable Cox regression and stratification analysis as well as functional enrichment analysis.ResultsWe detected a novel lncRNA-focus expression signature (LFES) consisting of 11 lncRNAs that were associated with survival based on risk scoring strategy in UCEC. The risk score based on the LFES was able to separate patients of discovery cohort into high-risk and low-risk groups with significantly different overall survival and progression-free survival, and has been successfully confirmed in the validation cohort. Furthermore, the LFES is an independent prognostic predictor of survival and demonstrates superior prognostic performance compared with the clinical covariates for predicting 5-year survival (AUC = 0.887). Functional analysis has linked the expression of prognostic lncRNAs to well-known tumor suppressor or ontogenetic pathways in endometrial carcinogenesis.ConclusionsOur study revealed a novel 11-lncRNA signature to predict survival of UCEC patient. This lncRNA signature may be a valuable and alternative marker for risk evaluation to aid patient-tailored treatment and improve the outcome of patients with UCEC.

Highlights

  • Endometrial cancer (UCEC) is a complex malignant tumor characterized by both genetic level and clinical trial

  • Further confirmation of long non-coding RNAs (lncRNAs)-focus expression signature (LFES) for survival prediction in the validation cohort and entire The Cancer Genome Atlas (TCGA) cohort To validate the universality of LFES for identification of uterine corpus endometrial carcinoma (UCEC) patients with poor outcome, we examined the ability of LFES in the independent validation cohort

  • The results indicated no significant difference in the distribution of expression levels for all 11 prognostic lncRNAs across four UCEC subtypes (Additional file 2), implying that the LFES is not a subtype-specific marker

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Summary

Introduction

Endometrial cancer (UCEC) is a complex malignant tumor characterized by both genetic level and clinical trial. The aim of this study was to access the prognostic value of long non-coding RNAs (lncRNAs) in UCEC patients and to identify potential lncRNA signature for predicting patients’ survival and improving patient-tailored treatment. Endometrial cancer, referred to as uterine corpus endometrial carcinoma (UCEC), is one of the most common gynecologic malignancy in the world with an increasing trend in recent years [1]. Recent studies have highlighted the clinical implications of lncRNAs as potential prognostic/diagnostic biomarkers or therapeutic targets in multiple cancers [11, 12].

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