The online version of this article (https://doi.org/10.1186/s12885-017-3983-0) contains supplementary material, which is available to authorized users.
Endometrial 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.
We 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.
We 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.
Our 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.
Additional file 1: lncRNAs significantly associated with overall survival in univariate Cox regression analyses. (DOC 38 kb)12885_2017_3983_MOESM1_ESM.doc
Additional file 2: Expression map of the 11 prognostic lncRNAs across four UCEC subtypes. Kruskal-Wallis test was used to compare expression levels for each lncRNAs across four UCEC subtypes. (DOC 765 kb)12885_2017_3983_MOESM2_ESM.doc
Leslie KK, Thiel KW, Goodheart MJ, De Geest K, Jia Y, Yang S. Endometrial cancer. Obstet Gynecol Clin N Am. 2012;39(2):255–68. CrossRef
Cancer Genome Atlas Research N, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, Shen H, Robertson AG, Pashtan I, Shen R, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73. CrossRef
Huang d W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13. CrossRef
Stefansson IM, Raeder M, Wik E, Mannelqvist M, Kusonmano K, Knutsvik G, Haldorsen I, Trovik J, Oyan AM, Kalland KH, et al. Increased angiogenesis is associated with a 32-gene expression signature and 6p21 amplification in aggressive endometrial cancer. Oncotarget. 2015;6(12):10634–45. CrossRefPubMedPubMedCentral
Zhou M, Zhang Z, Zhao H, Bao S, Cheng L, Sun J. An immune-related six-lncRNA signature to improve prognosis prediction of glioblastoma Multiforme. Mol Neurobiol. 2017. https://doi.org/10.1007/s12035-017-0572-9.
- A novel lncRNA-focus expression signature for survival prediction in endometrial carcinoma
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II