Glutamine metabolism reprogramming promotes bladder cancer progression via PYCR1: a multi-omics and functional...

Area of Science:

• Oncology
• Metabolic Reprogramming
• Immunotherapy

Background:

• Bladder cancer (BLCA) is a common malignancy with poor prognosis in advanced stages.
• Immune checkpoint inhibitors (ICIs) show promise, but predicting patient response is challenging.
• Glutamine metabolism's role in BLCA progression and immune modulation is poorly understood.

Purpose of the Study:

• To explore glutamine metabolism in BLCA.
• To identify its association with clinical outcomes and immunotherapy response.
• To functionally validate key regulatory genes.

Main Methods:

• Integrated analysis of metabolomics, single-cell RNA sequencing, and bulk transcriptomics.
• Development of a glutamine metabolism-based prognostic model (GMscore).
• Functional validation using in vitro and in vivo assays.

Main Results:

• Increased glutamine metabolism observed in BLCA.
• GMscore accurately predicted survival and immunotherapy response (lower score = better response).
• PYCR1 identified as a key regulator, promoting proliferation and tumor growth via proline synthesis and PI3K/AKT/mTOR pathway.

Conclusions:

• Comprehensive analysis of glutamine metabolism in BLCA.
• Introduction of a clinically relevant prognostic model (GMscore).
• PYCR1 identified as a critical metabolic regulator in BLCA development.