南方医科大学学报2025，Vol.45Issue(4)：880-892,13.DOI:10.12122/j.issn.1673-4254.2025.04.24
PYCR1的泛癌分析及其对膀胱癌化疗和免疫治疗应答的潜在预测价值
A pan-cancer analysis of PYCR1 and its predictive value for chemotherapy and immunotherapy responses in bladder cancer
摘要
Abstract
Objective 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).Conclusion 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.关键词
膀胱癌/吡咯啉-5-羧酸还原酶-1/免疫治疗/化疗药物敏感性/小分子PYCR1抑制剂Key words
bladder cancer/pyrroline-5-carboxylate reductase 1/immunotherapy/chemotherapy drug sensitivity/small molecule PYCR1 inhibitors引用本文复制引用
李煜桐,宋杏钰,孙蕊旭,董璇,刘宏伟..PYCR1的泛癌分析及其对膀胱癌化疗和免疫治疗应答的潜在预测价值[J].南方医科大学学报,2025,45(4):880-892,13.基金项目
广东省基础与应用基础研究基金(2024A1515012742) （2024A1515012742）
广东医科大学大学生创新创业训练计划项目(GDMU2023048,GDMU2023355,S202410571048) （GDMU2023048,GDMU2023355,S202410571048）
