A pan-cancer analysis of PYCR1 and its predictive value for chemotherapy and immunotherapy responses in bladder cancer.
10.12122/j.issn.1673-4254.2025.04.24
- Author:
Yutong LI
1
;
Xingyu SONG
1
;
Ruixu SUN
1
;
Xuan DONG
1
;
Hongwei LIU
1
Author Information
1. Laboratory of Urology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
- Publication Type:Journal Article
- Keywords:
bladder cancer;
chemotherapy drug sensitivity;
immunotherapy;
pyrroline-5-carboxylate reductase 1;
small molecule PYCR1 inhibitors
- MeSH:
Humans;
Urinary Bladder Neoplasms/genetics*;
Immunotherapy;
Prognosis;
Pyrroline Carboxylate Reductases/metabolism*;
Biomarkers, Tumor/genetics*;
delta-1-Pyrroline-5-Carboxylate Reductase;
Microsatellite Instability;
Tumor Microenvironment;
Mutation;
Computational Biology;
Molecular Docking Simulation
- From:
Journal of Southern Medical University
2025;45(4):880-892
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the potential of pyrroline-5-carboxylate reductase 1 (PYCR1) as a pan-cancer biomarker and investigate its expression, function, and clinical significance in bladder cancer (BLCA).
METHODS:Bioinformatics analysis was conducted to evaluate the associations of PYCR1 with prognosis, immune microenvironment remodeling, tumor mutation burden (TMB), and microsatellite instability (MSI) in cancer patients. Using the TCGA-BLCA dataset, univariate and multivariate regression analyses were performed to assess the potential of PYCR1 as an independent prognostic risk factor for BLCA, and a clinical decision model was constructed. The IMvigor210 cohort was utilized to evaluate the potential of PYCR1 for independently predicting the efficacy of immunotherapy. The pRRophetic was employed to screen candidate chemotherapeutic agents for treating BLCA with high PYCR1 expression. The CMap-XSum algorithm and molecular docking techniques were used to explore and validate small molecule inhibitors of PYCR1.
RESULTS:A high expression of PYCR1 was significantly associated with poor prognosis, immune cell infiltration, TMB and MSI in various tumors (r>0.3). PYCR1 was overexpressed in BLCA, and high PYCR1 expression was closely related to poor prognosis in BLCA patients (HR: 1.14, 95% CI: 1.02-1.68, P=0.006). The IC50 of the anti-cancer drugs cetuximab, 5-fluorouracil, and doxorubicin increased significantly in BLCA cell lines with high PYCR1 expressions (P<0.0001).
CONCLUSIONS:High PYCR1 expression is an independent risk factor for poor prognosis in BLCA patients and can serve as a significant indicator for clinical decision-making as well as a marker for predicting sensitivity to chemotherapeutic agents and the efficacy of immunotherapy.
