A survival model for prognostic prediction based on ferroptosis-associated genes and the association with immune infiltration in lung squamous cell carcinoma

Abstract

Lung squamous cell carcinoma (LUSC) is the primary pathological type of lung cancer with a less favorable prognosis. This study attempts to construct a ferroptosis-associated signature associated with overall survival (OS) that can predict the prognosis of LUSC and explore its relationship with immune infiltration. A 5 ferroptosis-associated gene model was constructed by LASSO-penalized regression analysis to predict the prognosis of patients with LUSC in the TCGA database and validated in the GEO and TCGA databases. Patients were stratified into high-risk and low-risk groups by the median value of the risk scores, and the former prognosis was significantly worse (P<0.001). Additionally, we found a certain association between the two risk groups and immune infiltration through CIBERSORT. Meanwhile, the differentially expressed genes (DEGs) between normal and tumor tissue were used to perform functional analysis, which showed a significant association with leukocyte transendothelial migration pathways in the TCGA cohort. In addition, immune cell infiltration analysis confirmed that M2 macrophages were significantly highly expressed in the high-risk group. Overall, the model successfully established by ferroptosis-associated genes suggests that ferroptosis may be related to immune infiltration in LUSC.

Ferroptosis in lung cancer: dual role, multi-level regulation, and new therapeutic strategies

“…Ferroptosis can promote tumor growth, proliferation, and help it evade immune surveillance through a variety of mechanisms. Particularly in lung cancer studies, ferroptosis appears to have a correlation with immune infiltration in LUSC, where the process of leukocyte transendothelial migration leads to modulation of M2 macrophages, ensuring their proficient infiltration within the immune microenvironment, thereby exerting an immunosuppressive role and propelling LUSC progression ( 58 ). A notable inverse relationship is observed between the majority of immune checkpoint proteins and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression.…”