A Novel E3-ubiquitin Ligase-Related LncRNA Signature for Predicting Prognosis in Patients with Lung Adenocarcinoma

Abstract

Background: E3 ubiquitin ligase mRNA plays an important role in mediating tumor microenvironment, and is involved in tumor initiation and progression. However, few studies have realized the value of E3 ubiquitin ligase-related lncRNAs in lung adenocarcinoma (LUAD).Methods: Herein, we comprehensively evaluated the E3-ubiquitination patterns including multiple tumor-related molecular phenotypes in LUAD samples using lncRNA profiling from GEO and TCGA database, identified a survival-related risk signature consisting of E3-ubiquitin ligase-related lncRNAs via LASSO and multivariate stepwise Cox regression analysis. Based on the risk score calculated for each sample, LUAD patients were divided into high- and low-risk groups. The predictive value of the signature in overall survival was explored, and a nomogram integrating the risk signature and clinical characteristics was identified and tested. Results: A risk signature consisting of 7 specific E3-ubiquitin ligase-related lncRNAs was screened, and can be viewed as a reliable independent predictor of prognosis. We performed consensus clustering analysis and successfully identified 4 molecular subtypes significantly linked to the OS of LUAD, which validates the prognostic and predictive value of this signature to some extent. The ssGESA analysis revealed that the high-risk group was bound up closely with epithelial-mesenchymal transition, hypoxia, and PI3K/AKT/mTOR pathways, and had a worse outcome. Moreover, we created a nomogram consisting of pathological staging and risk score. Validation analysis demonstrated high conformity of nomogram predictive probability and actual overall survival in LUAD of TCGA and GEO datasets.Conclusion: The model consisting of specific E3-ubiquitin ligase-related lncRNAs contributes to predicting the prognosis of LUAD patients.