Identification of a Novel Oxidative Stress- and Anoikis-Related Prognostic Signature and Its Immune Landscape Analysis in Non-Small Cell Lung Cancer

Abstract

The objective of this study was to identify a kind of prognostic signature based on oxidative stress- and anoikis-related genes (OARGs) for predicting the prognosis and immune landscape of NSCLC. Initially, We identified 47 differentially expressed OARGs that primarily regulate oxidative stress and epithelial cell infiltration through the PI3K-Akt pathway. Subsequently, 10 OARGs related to prognosis determined two potential clusters. A cluster was associated with a shorter survival level, lower immune infiltration, higher stemness index and tumor mutation burden. Next, The best risk score model constructed by prognostic OARGs was the Random Survival Forest model, and it included SLC2A1, LDHA and PLAU. The high-risk group was associated with cluster A and poor prognosis, with a higher tumor mutation burden, stemness index and proportion of M0-type macrophages, and a lower immune checkpoint expression level, immune function score and IPS score. The calibration curve and decision-making curve showed that the risk score combined with clinical pathological characteristics could be used to construct a nomogram for guiding the clinical treatment strategies. Finally, We found that all three hub genes were highly expressed in tumor tissues, and LDHA expression was mainly regulated by has-miR-338-3p, has-miR-330-5p and has-miR-34c-5p. Altogether, We constructed an OARG-related prognostic signature to reveal potential relationships between the signature and clinical characteristics, TME, stemness, tumor mutational burden, drug sensitivity and immune landscape in NSCLC patients.