P-318 TLE3-AKR1B1 signaling axis participating in the malignant progression of gastrointestinal stromal tumor by regulating galactose metabolism

KIT and / or PDGFRA activation mutation is the initial molecular event of gastrointestinal stromal tumor (GIST), mechanism leading to malignant progression GIST needs be further studied broken through. This study aims understand from perspective metabolic reprogramming provide a new target for treatment GIST. In present study, transcriptome metabolome were used test tissue adjacent normal samples with different degrees malignancy. Galactose metabolism its rate-limiting enzyme AKR1B1 involved in through combined analysis transcriptome, targeted proteome metabolome. Expression AKR1B1, correlation patients’ prognosis analyzed using immumohistochemical staining, followed determination function underlying mechanism. was upregulated by regulating galactose metabolism. The transcription factor TLE3 inhibits cell proliferation mitosis targeting AKR1B1. Analysis between expression shows that are abnormally expressed GIST, can negatively regulate which closely related patients. Epalrestat, small molecule inhibitor metabolites lactose, inositol, sucrose, UDP-d-galactose D-mannitol pathway, redirection flux branches pathway cope inhibition maintain dynamic balance TLE3-AKR1B1 signaling axis participate regulation metabolism, providing experimental data understanding reprogramming, also treatment.