This research presents a comprehensive proteogenomic analysis of gallbladder cancer (GBC) to uncover the molecular drivers of its high mortality and clinical diversity. By integrating genomic, transcriptomic, and proteomic data, the authors identified four distinct molecular subtypes and four immune microenvironment profiles that correlate with patient prognosis and drug sensitivity. A key discovery involves the role of metabolic reprogramming, specifically through proteins like ACAT1 and PHGDH, in fueling the liver invasion that characterizes advanced disease. The study also explores the rare neuroendocrine variant of GBC, identifying the transcription factor MEIS1 as a critical regulator of cellular transdifferentiation. These findings establish a therapeutic framework aimed at personalizing treatment strategies, such as combining immunotherapy with metabolic or kinase inhibitors. Ultimately, the data provides a high-resolution map of the GBC landscape to assist in the development of targeted clinical interventions.

References:

• Fu Z, Song Y, Liu F, et al. Integrative proteogenomic analysis provides molecular insights and clinical significance in gallbladder cancer[J]. Cancer Cell, 2026.