Metabolic Rewiring Linked to FGFR3 Gene Alterations in Bladder Cancer: A Multi-Omics Systems Metabolomics Approach
Bladder cancer is one of the most common malignancies worldwide, highly impacting public health systems due to its chronicity and recurrence, and metabolic alterations can offer an opportunity to identify novel, urgently needed, prognostic markers and therapeutic vulnerabilities for precision oncology. Here, we applied a systems metabolomic approach, based on the integration of metabolically functional data and multi-omics datasets, including transcriptomics and exometabolomics, through biostatistical analysis and mathematical modelling, to characterize the metabolic rearrangements associated with the most frequent lesion in bladder cancer, the oncogenic activation of FGFR3 gene. The analyses were performed on a panel of six human bladder cancer cell lines at different stages and grades, stratified based on the presence of FGFR3 alterations. The analysis revealed an interesting correlation between FGFR3 alteration and the acquisition of a predominantly oxidative, poorly migratory phenotype, regardless of the stage of tumor progression. The preclinical results were validated on a large publicly available dataset of muscle-invasive bladder cancer patient samples.