Predictive and therapeutic value of the ferroptosis gene CISD1 in non?small cell lung cancer.

Abstract

The present study aimed to investigate the expression of ferroptosis genes in non-small cell lung cancer and their relationship with prognosis, and to analyze the relationship between ferroptosis genes and tumor immunity. To evaluate the expression levels of ferroptosis genes and their association with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), The Cancer Genome Atlas LUAD and LUSC data were downloaded, patient clinical information and ferroptosis gene expression profiles were extracted, and differential gene expression, survival and correlation analyses were performed using R. Using immune correlation analysis, the value of ferroptosis genes for immunotherapy was explored. The potential application of ferroptosis genes in immunotherapy was further validated by immunohistochemical staining. A number of ferroptosis-associated genes were differentially expressed in tumor tissues compared with in non-tumor tissues. CDGSH iron-sulfur domain-containing protein 1 (CISD1) was upregulated in both LUAD and LUSC tumor tissues, and was associated with tumor Tumor-Node-Metastasis stage. Notably, high levels of CISD1 in LUAD indicated a poor prognosis, and CISD1 was negatively correlated with CD4⁺ T cells based on the immune score. Furthermore, CISD1 may be involved in pathways such as cellular response to hypoxia, DNA repair, extracellular matrix-related genes, epithelial-mesenchymal transition markers, oxidative phosphorylation and PI3K-AKT-mTOR pathway. Immunohistochemical staining indicated that CISD1 was highly expressed in LUAD tissues, it was associated with a poor prognosis of patients with LUAD, and it was negatively associated with CD4 and CD20. In conclusion, the ferroptosis gene CISD1 may be associated with the prognosis of LUAD, and high levels of CISD1 could indicate a shorter survival time. Furthermore, CISD1 has potential applications in immunotherapy. These findings may provide novel theoretical insights into the treatment of LUAD.