Chen Yanfei, Xian Peiyi, Lu Jianming, Zhang Le, Cai Chao, Zhong Weide
Department of Urology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
School of Medicine, Jinan University, Guangzhou, China.
Clin Med Insights Oncol. 2025 Aug 10;19:11795549251359145. doi: 10.1177/11795549251359145. eCollection 2025.
This study investigates the potential of purine nucleoside phosphorylase (PNP) as a biomarker and therapeutic target in muscle-invasive bladder cancer (MIBC). We aimed to explore PNP's expression, prognostic value, and role in metabolic pathways, along with its association with gene mutations.
We conducted multi-omics analyses using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases to evaluate PNP expression across MIBC samples and its prognostic impact through Kaplan-Meier and Cox regression analyses. Functional enrichment and gene set variation analysis (GSVA) were performed to identify PNP-related pathways. In addition, siRNA knockdown experiments were carried out to assess PNP's influence on MIBC cell proliferation.
Our findings revealed that PNP is significantly overexpressed in MIBC tissues and serves as an independent prognostic factor, correlating with poor clinical outcomes across multiple cohorts (TCGA: hazard ratio [HR] > 1.3, < .05; GSE48075: HR > 1.5, = .07; GSE169455: HR > 2.8, < .001). Functional enrichment analysis identified PNP's involvement in various metabolic pathways. Furthermore, we observed a high frequency of RB1 mutations in the PNP-high expression group. Based on this observation, we hypothesize that patients harboring RB1 mutations may benefit from PNP-targeted therapy. In vitro experiments demonstrated that PNP knockdown significantly reduces MIBC cell proliferation.
This study underscores PNP's role as a promising biomarker and therapeutic target in MIBC.
本研究调查嘌呤核苷磷酸化酶（PNP）作为肌肉浸润性膀胱癌（MIBC）生物标志物和治疗靶点的潜力。我们旨在探索PNP的表达、预后价值及其在代谢途径中的作用，以及它与基因突变的关联。
我们使用来自癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）和其他公共数据库的数据进行多组学分析，以评估MIBC样本中PNP的表达，并通过Kaplan-Meier和Cox回归分析评估其预后影响。进行功能富集和基因集变异分析（GSVA）以识别与PNP相关的途径。此外，进行了小干扰RNA（siRNA）敲低实验，以评估PNP对MIBC细胞增殖的影响。
我们的研究结果显示，PNP在MIBC组织中显著过表达，并且是一个独立的预后因素，与多个队列中的不良临床结果相关（TCGA：风险比[HR]>1.3，P<0.05；GSE48075：HR>1.5，P=0.07；GSE169455：HR>2.8，P<0.001）。功能富集分析确定PNP参与各种代谢途径。此外，我们在PNP高表达组中观察到RB1突变的高频率。基于这一观察结果，我们假设携带RB1突变的患者可能从PNP靶向治疗中获益。体外实验表明，PNP敲低显著降低MIBC细胞增殖。
本研究强调了PNP作为MIBC中有前景的生物标志物和治疗靶点的作用。
