Identification of two molecular subtypes and a novel prognostic model of lung adenocarcinoma based on a cuproptosis-associated gene signature

Lung adenocarcinoma is the most common subtype of lung cancer clinically, with high mortality and poor prognosis. Cuproptosis present a newly discovered mode of cell death characterized by aggregation of fatty acylated proteins, depletion of iron-sulfur clusterin, triggering of HSP70, and induction of intracellular toxic oxidative stress. However, the impact of cuproptosis on lung adenocarcinoma development, prognosis, and treatment has not been elucidated. By systematically analyzing the genetic alterations of 10 cuproptosis-related genes in lung adenocarcinoma, we found that CDKN2A, DLAT, LIAS, PDHA1, FDX1, GLS, and MTF1 were differentially expressed between lung cancer tissues and adjacent tissues. Based on the expression levels of 10 cuproptosis-related genes, we classified lung adenocarcinoma patients into two molecular subtypes using the Consensus clustering method, of which subtype 2 had a worse prognosis. Differential expression genes associated with prognosis between the two subtypes were obtained by differential analysis and survival analysis, and cox lasso regression was applied to construct a cuproptosis-related prognostic model. Its survival predicting ability was validated in three extrinsic validation cohorts. The results of multivariate cox analysis indicated that cuproptosis risk score was an independent prognostic predictor, and the mixed model formed by cupproptosis prognostic model combined with stage had more robust prognostic prediction accuracy. We foun...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research