Ferroptosis-related genes DUOX1 and HSD17B11 affect tumor microenvironment and predict overall survival of lung adenocarcinoma patients

• Published in: Medicine (Baltimore) 2024-05, Vol.103 (22), p.e38322
• Main Authors: Wei, Chunhui, Li, Lixia, Qiao, Youping, Chen, Yujuan, Zhang, Chunfeng, Xie, Jinye, Fang, Jiayan, Liang, Zhu, Huang, Dan, Wu, Dong
• Format: Article
• Language: English
• Subjects: 20-Hydroxysteroid Dehydrogenases; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Dual Oxidases - genetics; Estradiol Dehydrogenases - genetics; Female; Ferroptosis - genetics; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Prognosis; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology
• ISSN: 0025-7974; 1536-5964; 1536-5964
• DOI: 10.1097/MD.0000000000038322

Recent studies have found that ferroptosis-related genes (FRGs) have broad applications in tumor therapy. However, the predictive potential of these genes in lung adenocarcinoma (LUAD) remains to be fully characterized. We aimed to investigate the FRGs that might be potential targets for LUAD. We screened the RNA sequencing samples from LUAD patients from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of DEGs was performed. The risk model was constructed to evaluation and validation FRGs. We explored the immune landscape of LUAD and controls. The value of FRGs in diagnosing LUAD was tested in the GSE30219, GSE37745, GSE0081 datasets, and qPCR was used to verify their diagnostic value in LUAD patients in our hospital. A total of 1327 DEGs in quantitative proteomics were obtained, of which ferroptosis-related DEGs were 259. Enrichment analysis showed significant enrichment in the absorption and metabolism of fatty acids and arachidonic acid. The upregulated genes (GCLC, RRM2, AURKA, SLC7A5, and SLC2A1) and downregulated genes (ANGPTL7, ALOX15, ALOX15B, HSD17B11, IL33, TSC22D3, and DUOX1) were selected as core genes in tissue samples from 62 patients by qPCR. DUOX1 and HSD17B11 were obtained by bioinformatics analysis, both of which showed similar expression trends at the RNA and protein levels. The Kaplan-Meier method showed that DUOX1 and HSD17B11 were closely related to the overall survival (OS) of LUAD patients. Ferroptosis-related genes DUOX1 and HSD17B11 are of considerable value in the diagnosis of LUAD patients. Their low expression suggests an increased recurrence rate and leads to a decrease in the patient quality of life.