Bioinformatics and Experimental Validation for Identifying Biomarkers Associated with AMG510 (Sotorasib) Resistance in KRAS^G12C-Mutated Lung Adenocarcinoma.

ABSTRACT: The Kirsten rat sarcoma viral oncogene homolog (KRAS)^G12C mutation is prevalent in lung adenocarcinoma (LUAD), driving tumor progression and indicating a poor prognosis. While the FDA-approved AMG510 (Sotorasib) initially demonstrated efficacy in treating KRAS^G12C-mutated LUAD, resistance emerged within months. Data from AMG510 treatment-resistant LUAD (GSE204753) and single-cell datasets (GSE149655) were analyzed. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to explore enriched signaling pathways, nomogram models were constructed, and transcription factors predicting resistance biomarkers were predicted. CIBERSORT identified immune cell subpopulations, and their association with resistance biomarkers was assessed through single

SUBMITTER: Lin P 

PROVIDER: S-EPMC10855101 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature