DLAT suppresses tumor progression and modulates treatment response in colorectal cancer: Insights from a metabolic prognostic model.

[BACKGROUND] Metabolic reprogramming is a hallmark of cancer and offers promising therapeutic targets. Disrupting core metabolic pathways may impair energy supply and biosynthetic processes in tumor cells, providing new strategic insights for colorectal cancer (CRC) treatment.

[METHODS] We integrated metabolism-associated genes and applied LASSO regression to identify core prognostic genes. A metabolic risk model was developed and validated using public datasets. Analyses included survival, functional enrichment, immune infiltration, and drug sensitivity. Lentivirus-mediated DLAT overexpression was used for in vitro validation to assess migration, invasion, proliferation, drug response, cell cycle, and apoptosis.

[RESULTS] The risk model stratified CRC patients into high- and low-risk groups, with significantly worse overall survival in the high-risk group. Functional analysis revealed enrichment in cell cycle, immune response, inflammation, and metabolic pathways. The high-risk group showed reduced infiltration of B cells, T cells, NK cells, and dendritic cells. Drug-sensitivity analysis indicated higher IC50 values for chemotherapy and targeted agents in high-risk patients, suggesting broad resistance. In vitro, DLAT overexpression suppressed migration, invasion, and proliferation, enhanced chemosensitivity, induced cell cycle arrest, and promoted apoptosis.

[CONCLUSIONS] DLAT plays a critical role in CRC progression and treatment response, demonstrating potential as a prognostic biomarker and therapeutic target.