Development and validation of a prognostic nomogram for patients with lung adenocarcinoma based on a novel 6-DNA repair-related gene signature

Am J Transl Res. 2021 Apr 15;13(4):1952-1970. eCollection 2021.

Abstract

DNA repair-related genes (DRGs) have attracted much attention in the field of oncology. However, the prognostic role of DRGs and their biological function in lung adenocarcinoma (LUAD) remains rudimentary and inconclusive. In this study, 716 LUAD cases from two different cohorts were collected. Samples from The Cancer Genome Atlas (TCGA) were used as the training set, and data from Gene Expression Omnibus (GEO) datasets were used for validation. Using multivariate Cox analysis and LASSO regression, we constructed a DRG signature and used it, together with clinical indices, to develop a nomogram to predict 1-, 3-, and 5-year survival rates. We identified a six-DRG signature to estimate the survival of LUAD patients, which distinguished high-risk from low-risk patients with LUAD in both the training and validation cohorts. We also observed elevated levels of infiltrating CD4 memory activated T cells, resting NK cells, M0 and M1 macrophages, and activated mast cells in the high-risk group. Finally, a nomogram incorporating the signature and clinical parameters was superior to the American Joint Committee on Cancer (AJCC) staging system in predicting the survival of LUAD patients. The DRG prognostic signature and integrated nomogram could be a useful tool to predict prognosis in patients with LUAD.

Keywords: DNA repair genes; Lung adenocarcinoma; nomogram; personalized prediction model; prognosis.