Multi-omics reveals AKR1B1-regulated galactose metabolic as a driver of gastrointestinal stromal tumor progression

Abstract

The underlying mechanism of malignant progression in gastrointestinal stromal tumors (GISTs) is not fully understood. Despite recent advancements, a comprehensive profile of metabolome, transcriptome, and proteome of GISTs is lacking. This study conducted an integrated multi-omics analysis of GISTs across different risk classifications. By integrating metabolomics, transcriptomics, and proteomics, we identify distinct metabolic patterns and associated biological pathways implicated in the malignant progression of GISTs. Moreover, we identified galactose metabolism and the pivotal rate-limiting enzyme AKR1B1 is dysregulated in GISTs progression. AKR1B1 was upregulated and predicted poor prognosis in GISTs. In addition, AKR1B1 knockdown resulted in trehalose accumulation in GIST cells, thereby inhibiting cell proliferation and mitosis. These findings not only enhance our comprehension of the underlying mechanisms governing GIST progression from a metabolic reprogramming standpoint but also furnish prognostic biomarkers and potential therapeutic targets for GISTs.