Exploring Key Genes Related to Ferroptosis Amino Acid Metabolism in Lung Adenocarcinoma Based on Transcriptome Data

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Abstract

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. GOT1 overexpression correlated with advanced tumor stage (P<0.05), metastasis (P<0.05), and poor survival (log-rank P<0.05). Functional studies demonstrated that GOT1 knockdown suppressed LUAD cell proliferation , migration, and induced apoptosis, while reducing tumor growth in vivo (P<0.001). Conversely, CDO1 exhibited tumor-suppressive effects, with a negative correlation to GOT1 (Pearson r=-0.42, P=0.008). Finally,A prognostic model incorporating GOT1 showed strong predictive accuracy (C-index=0.72). These findings establish ​GOT1​ as a critical driver of LUAD progression through ferroptosis-amino acid metabolic reprogramming, highlighting its potential as a therapeutic target and prognostic biomarker. The antagonistic roles of GOT1 and CDO1 provide new insights into metabolic regulation in LUAD, paving the way for precision therapy strategies.

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