Development and Validation of a Seven-Gene Signature for Predicting the Prognosis of Lung Adenocarcinoma.

Abstract

Background Prognosis is a main factor affecting the survival of patients with lung adenocarcinoma (LUAD), yet no robust prognostic model of high effectiveness has been developed. This study is aimed at constructing a stable and practicable gene signature-based model via bioinformatics methods for predicting the prognosis of LUAD sufferers. Methods The mRNA expression data were accessed from the TCGA-LUAD dataset, and paired clinical information was collected from the GDC website. R package “edgeR” was employed to select the differentially expressed genes (DEGs), which were then used for the construction of a gene signature-based model via univariate COX, Lasso, and multivariate COX regression analyses. Kaplan-Meier and ROC survival analyses were conducted to comprehensively evaluate the performance of the model in predicting LUAD prognosis, and an independent dataset GSE26939 was accessed for further validation. Results Totally, 1,655 DEGs were obtained, and a 7-gene signature-based risk score was developed and formulated as risk_score = 0.000245∗NTSR1 + (7.13E − 05)∗RHOV + 0.000505∗KLK8 + (7.01E − 05)∗TNS4 + 0.000288∗C1QTNF6 + 0.00044∗IVL + 0.000161∗B4GALNT2. Kaplan-Meier survival curves revealed that the survival rate of patients in the high-risk group was lower in both the TCGA-LUAD dataset and GSE26939 relative to that of patients in the low-risk group. The relationship between the risk score and clinical characteristics was further investigated, finding that the model was effective in prognosis prediction in the patients with different age (age > 65, age < 65) and TNM stage (N0&N1, T1&T2, and tumor stage I/II). In sum, our study provides a robust predictive model for LUAD prognosis, which boosts the clinical research on LUAD and helps to explore the mechanism underlying the occurrence and progression of LUAD.