Redox-associated messenger RNAs identify novel prognostic values and influence the tumor immune microenvironment of lung adenocarcinoma

Abstract

Background: An imbalance of redox homeostasis participates in tumorigenesis, proliferation, and metastasis, which results from the production of reactive oxygen species (ROS). However, the biological mechanism and prognostic significance of redox-associated messenger RNAs (ramRNAs) in lung adenocarcinoma (LUAD) still remain unclear.Methods: Transcriptional profiles and clinicopathological information were retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) of LUAD patients. A total of 31 overlapped ramRNAs were determined, and patients were separated into three subtypes by unsupervised consensus clustering. Biological functions and tumor immune-infiltrating levels were analyzed, and then, differentially expressed genes (DEGs) were identified. The TCGA cohort was divided into a training set and an internal validation set at a ratio of 6:4. Least absolute shrinkage and selection operator regression were used to compute the risk score and determine the risk cutoff in the training set. Both TCGA and GEO cohort were distinguished into a high-risk or low-risk group at the median cutoff, and then, relationships of mutation characteristics, tumor stemness, immune differences, and drug sensitivity were investigated.Results: Five optimal signatures (ANLN, HLA-DQA1, RHOV, TLR2, and TYMS) were selected. Patients in the high-risk group had poorer prognosis, higher tumor mutational burden, overexpression of PD-L1, and lower immune dysfunction and exclusion score compared with the low-risk group. Cisplatin, docetaxel, and gemcitabine had significantly lower IC50 in the high-risk group.Conclusion: This study constructed a novel predictive signature of LUAD based on redox-associated genes. Risk score based on ramRNAs served as a promising biomarker for prognosis, TME, and anti-cancer therapies of LUAD.