Prognostic value and immunological function of cuproptosis-related genes in lung adenocarcinoma.

ABSTRACT

Background: Lung cancer is one of the malignant tumors with the highest morbidity and fatality rates worldwide. The overall survival (OS) of lung adenocarcinoma (LUAD) is poor. Cuproptosis is a copper-triggered modality of mitochondrial cell death, however, its contribution to the emergence of lung cancer is unknown. The clinical implication and immunological function of cuproptosis-related genes (CRGs) in LUAD has yet to be established. Methods: TCGA, HPA, GEPIA, Kaplan-Meier, TIMER and CancerSEA database were used to explore the prognostic value and biological function of CRGs in LUAD. Results: CRGs are primarily involved in copper ion transport, the citrate cycle (TCA cycle) and central carbon metabolism in LUAD. The mRNA expression of COA6, UBE2D1, DLAT, SLC25A3, and DBH was significantly increased. The expression of COA6, DLAT, SLC25A3, DBH, and LOXL2 were all strongly associated with the clinicopathological stages in LUAD. Moreover, high expression of COA6, UBE2D1, DLAT, SLC25A3 and LOXL2 was related to poor OS. The expression of SLC25A3 and LOXL2 showed different association with immune cell infiltration. The single cell sequencing demonstrated that CRGs play important roles in the regulation of DNA damage response, inflammation and metastasis in LUAD. Conclusions: In summary, this study comprehensively uncovered that CRGs could be identified as potential prognostic and immunological biomarkers in LUAD. Our current research could provide a solid theoretical basis for LUAD survival research and clinical decision-making.