Lung adenocarcinoma (LUAD) is a highly aggressive cancer with limited treatment options. This study investigated key genes linking ferroptosis and amino acid metabolism in LUAD using bioinformatics and experimental validation. Analysis of TCGA and GEO datasets identified GOT1 (upregulated) and CDO1 (downregulated) as core regulators. High GOT1 expression was associated with advanced clinicopathological characteristics and poor survival (log-rank P < 0.05). Functional studies demonstrated that GOT1 knockdown suppressed LUAD cell proliferation and clonogenic growth while promoting apoptosis, and also reduced tumor growth in vivo (P < 0.001). In addition, CDO1 showed an expression pattern consistent with a potentially protective role in LUAD and was inversely correlated with GOT1 (Spearman's R = - 0.177, P < 0.001). Finally, a prognostic model incorporating GOT1 showed strong predictive accuracy (C-index = 0.705). These findings highlight the important role of GOT1 in LUAD progression and suggest that it may contribute to ferroptosis-related amino acid metabolic reprogramming, supporting its potential as a prognostic biomarker and therapeutic target.
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