Discovery of Multiple Effects of Reactive Oxygen Species on Lung Adenocarcinoma at the Single-cell and Bulk Tissue Levels.

Abstract

Reactive oxygen species (ROS) are potential targets for treating malignant tumors. The aim of this study was to probe into the mechanisms of disease development and treatment in lung adenocarcinoma (LUAD). This study investigated the impact of ROS on the progression of LUAD at different transcriptomic levels and analyzed key molecules involved in the regulation of LUAD. Single-cell RNA-seq (scRNA-seq) data of LUAD were clustered and annotated to determine cell types. Scissor cells based on LUAD bulk transcriptome and epithelial scRNA-seq data were used to classify subsets associated with ROS phenotypes. Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate regression analyses were performed between the Scissor-positive and Scissor-negative epithelial cells to select key differentially expressed genes (DEGs) for developing a ROS-related signature. The ROS score was significantly negatively correlated with the overall survival (OS) of LUAD. Seven cell types from the LUAD tissues were identified. The ROS-related gene signature was significantly correlated with metabolism, tumor microenvironment (TME) indicators, and the half-maximal inhibitory concentration (IC50) values of 10 drugs. The gene signature was verified as an independent indicator for LUAD prognosis. The current study provided novel insights into the impact of ROS on LUAD pathology at both single-cell and bulk-tissue levels, facilitating the prognostic evaluation and drug therapy development for patients with LUAD.