The hypoxia-associated genes in immune infiltration and treatment options of lung adenocarcinoma

Abstract

Background Lung adenocarcinoma (LUAD) is a common lung cancer with a poor prognosis under standard chemotherapy. Hypoxia is a crucial factor in the development of solid tumors, and hypoxia-related genes (HRGs) are closely associated with the proliferation of LUAD cells. Methods In this study, LUAD HRGs were screened, and bioinformatics analysis and experimental validation were conducted. The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to gather LUAD RNA-seq data and accompanying clinical information. LUAD subtypes were identified by unsupervised cluster analysis, and immune infiltration analysis of subtypes was conducted by GSVA and ssGSEA. Cox regression and LASSO regression analyses were used to obtain prognosis-related HRGs. Prognostic analysis was used to evaluate HRGs. Differences in enrichment pathways and immunotherapy were observed between risk groups based on GSEA and the TIDE method. Finally, RT-PCR and in vitro experiments were used to confirm prognosis-related HRG expression in LUAD cells. Results Two hypoxia-associated subtypes of LUAD were distinguished, demonstrating significant differences in prognostic analysis and immunological characteristics between subtypes. A prognostic model based on six HRGs (HK1, PDK3, PFKL, SLC2A1, STC1, and XPNPEP1) was developed for LUAD. HK1, SLC2A1, STC1, and XPNPEP1 were found to be risk factors for LUAD. PDK3 and PFKL were protective factors in LUAD patients. Conclusion This study demonstrates the effect of hypoxia-associated genes on immune infiltration in LUAD and provides options for immunotherapy and therapeutic strategies in LUAD.

Keywords

• Hypoxia
• Lung adenocarcinoma
• Unsupervised clustering
• Prognostic
• Immunotherapy