Identification and Validation of a Novel Six-lncRNA-Based Prognostic Model for Lung Adenocarcinoma

Front Oncol. 2022 Jan 17:11:775583. doi: 10.3389/fonc.2021.775583. eCollection 2021.

Abstract

Objective: This study was conducted in order to establish a long non-coding RNA (lncRNA)-based model for predicting overall survival (OS) in patients with lung adenocarcinoma (LUAD).

Methods: Original RNA-seq data of LUAD samples were extracted from The Cancer Genome Atlas (TCGA) database. Univariate Cox survival analysis was performed to select lncRNAs associated with OS. The least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox analysis were performed for building an OS-associated lncRNA prognostic model. Moreover, receiver operating characteristic (ROC) curves were generated to assess predictive values of the hub lncRNAs. Consequently, qRT-PCR was conducted to validate its prognostic value. The potential roles of these lncRNAs in immunotherapy and anti-angiogenic therapy were also investigated.

Results: The lncRNA-associated risk score of OS (LARSO) was established based on the LASSO coefficient of six individual lncRNAs, including CTD-2124B20.2, CTD-2168K21.1, DEPDC1-AS1, RP1-290I10.3, RP11-454K7.3, and RP11-95M5.1. Kaplan-Meier analysis revealed that LUAD patients with higher LARSO values had a shorter OS. Furthermore, a new risk score (NRS), including LARSO, stage, and N stage, could better predict the prognosis of LUAD patients compared with LARSO alone. Evaluation of the prognostic model in our cohort demonstrated that patients with higher scores had a worse prognosis. In addition, correlation analysis between these six lncRNAs and immune checkpoints or anti-angiogenic targets suggested that LUAD patients with high LARSO might not be sensitive to immunotherapy or anti-angiogenic therapy.

Conclusions: This robust six-lncRNA prognostic signature may be used as a novel and powerful prognostic biomarker for lung adenocarcinoma.

Keywords: least absolute shrinkage and selection operator (LASSO); lncRNA; lung adenocarcinoma; overall survival; prognostic model.