Prediction of Clinical Outcome in Endometrial Carcinoma Based on a 3-lncRNA Signature

Abstract

Endometrial carcinoma (EC) is one of the common gynecological cancers with increasing incidence and revived mortality recently. Given the heterogeneity of tumors and the complexity of lncRNAs, a panel of lncRNA biomarkers might be more precise and stable for prognosis. In the present study, we developed a new lncRNA model to predict the prognosis of patients with EC. EC-associated differentially expressed long noncoding RNAs (lncRNAs) were identified from The Cancer Genome Atlas (TCGA). Univariate COX regression and least absolute shrinkage and selection operator (LASSO) model were selected to find the 8-independent prognostic lncRNAs of EC patient. Furthermore, the risk score of the 3-lncRNA signature for overall survival (OS) was identified as CTD-2377D24.6 expression × 0.206 + RP4-616B8.5 × 0.341 + RP11-389G6.3 × 0.343 by multivariate Cox regression analysis. According to the median cutoff value of this prognostic signature, the EC samples were divided into two groups, high-risk set (3-lncRNAs at high levels) and low-risk set (3-lncRNAs at low levels), and the Kaplan–Meier survival curves demonstrated that the low-risk set had a higher survival rate than the high-risk set. In addition, the 3-lncRNA signature was closely linked with histological subtype (p = 0.0001), advanced clinical stage (p = 0.011), and clinical grade (p < 0.0001) in EC patients. Our clinical samples also confirmed that RP4-616B8.5, RP11-389G6.3, and CTD-2377D24.6 levels were increased in tumor tissues by qRT-PCR and in situ hybridization. Intriguingly, the p-value of combined 3-lncRNAs was lower than that of each lncRNA, indicating that the 3-lncRNA signature also showed higher performance in EC tissue than paracancerous. Functional analysis revealed that cortactin might be involved in the mechanism of 3-lncRNA signatures. These findings provide the first hint that a panel of lncRNAs may play a critical role in the initiation and metastasis of EC, indicating a new signature for early diagnosis and therapeutic strategy of uterine corpus endometrial carcinoma.