Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Despite advances in treatment, the prognosis remains poor due to late diagnosis. Cuproptosis (driven by copper ion accumulation) and disulfidptosis (driven by disulfide bond accumulation) are novel forms of programmed cell death, closely linked to tumor initiation, progression, and resistance. However, the specific roles of these mechanisms in LUAD remain inadequately studied. This study integrated multi-omics data from TCGA and GEO databases to systematically evaluate the differential expression and prognostic significance of copper and disulfide-related genes (DCRGs), identify two DCRG molecular subtypes, and construct a DCRG scoring model based on four key genes. Multi-omics analysis results revealed that the DCRG score not only accurately predicts prognosis in LUAD patients but is also closely associated with immune cell infiltration patterns and EGFR inhibitor responses. RT-qPCR validated the high expression of FURIN and RHOV in LUAD cells, supporting their role as potential therapeutic targets. Further Mendelian randomization analysis confirmed the causal relationship between FURIN and LUAD development. These findings provide novel biomarkers for the prognosis evaluation of LUAD based on cuproptosis and disulfidptosis mechanisms and offer a theoretical basis for targeting FURIN in LUAD treatment.
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| http://dx.doi.org/10.1038/s41598-025-90653-5 | DOI Listing |
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