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A comprehensive analysis of metabolomics and transcriptomics reveals a novel crizotinib resistance mechanism in non-small cell lung cancer

ABSTRACT: Crizotinib is a first-line targeted therapy against EML4-ALK fusion in non-small cell lung cancer (NSCLC), but the increased resistance limits its clinical application. However, the mechanisms underlying such resistance are largely unexplored. The present study identified ALK protein overexpression in crizotinib-resistant H3122CR cells through immunoblotting. Then, liquid chromatography tandem mass spectrometry-based metabolomics was adopted to investigate metabolic responses. Crizotinib resistance was associated with the reduction of the total lipid content and the increase of organic acid, featuring the upregulation of lipid metabolism. Fatty acid β-oxidation pathway reprogrammed crizotinib-sensitive metabolome to crizotinib-resistant metabolome, resulting in crizotinib resistance. These findings reveal a previously unknown mechanism of crizotinib resistance and suggest promising applications of this approach in prognostic prediction and tailored therapeutics of NSCLC patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186767 | GEO | 2021/10/31

REPOSITORIES: GEO

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