Circulating metabolites and bladder cancer: a Mendelian randomization and multi-omics study

Area of Science:

• Metabolomics
• Genomics
• Oncology

Background:

• Mechanisms linking circulating metabolites to bladder cancer (BLCA) progression via gene expression are not well understood.
• Identifying these links is crucial for understanding BLCA pathogenesis.

Purpose of the Study:

• To investigate potential causal relationships between circulating metabolites and BLCA risk using Mendelian randomization (MR).
• To identify key metabolic pathways involved in BLCA development.
• To explore the interplay between metabolic dysregulation and genetic alterations in BLCA.

Main Methods:

• Employed bidirectional two-sample Mendelian randomization (MR) to assess metabolite-BLCA associations.
• Conducted rigorous methodological and sensitivity analyses for result robustness.
• Utilized KEGG pathway analysis and cross-referenced with TCGA/GEO datasets for gene-metabolite pathway links.

Main Results:

• Identified 27 circulating metabolites with causal links to BLCA (18 risk, 9 protective).
• Reverse MR confirmed metabolite-level influence on BLCA.
• Pathway analysis revealed 41 metabolic pathways, with 3 consistently altered in public datasets, illustrating connections between metabolic and genetic changes.

Conclusions:

• Established causal links between specific metabolites and BLCA, identifying significant metabolic pathways.
• Combined metabolomic and transcriptomic data offer novel insights into BLCA metabolomics.
• Findings provide a foundation for developing targeted metabolic interventions for BLCA.