Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer
Background: 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 muta...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-08-01
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| Series: | Clinical Medicine Insights: Oncology |
| Online Access: | https://doi.org/10.1177/11795549251359145 |
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| author | Yanfei Chen Peiyi Xian Jianming Lu Le Zhang Chao Cai Weide Zhong |
| author_facet | Yanfei Chen Peiyi Xian Jianming Lu Le Zhang Chao Cai Weide Zhong |
| author_sort | Yanfei Chen |
| collection | DOAJ |
| description | Background: 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. Methods: 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, in vitro siRNA knockdown experiments were carried out to assess PNP’s influence on MIBC cell proliferation. Results: 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, P < .05; GSE48075: HR > 1.5, P = .07; GSE169455: HR > 2.8, P < .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. Conclusion: This study underscores PNP’s role as a promising biomarker and therapeutic target in MIBC. |
| format | Article |
| id | doaj-art-3fb4e783806a45269700ff9db8d0974d |
| institution | Kabale University |
| issn | 1179-5549 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Oncology |
| spelling | doaj-art-3fb4e783806a45269700ff9db8d0974d2025-08-20T03:40:43ZengSAGE PublishingClinical Medicine Insights: Oncology1179-55492025-08-011910.1177/11795549251359145Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder CancerYanfei Chen0Peiyi Xian1Jianming Lu2Le Zhang3Chao Cai4Weide Zhong5School of Medicine, Jinan University, Guangzhou, ChinaThe Third Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, ChinaInstitute for Integrative Genome Biology, University of California, Riverside, CA, USAGuangdong Provincial Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Urology, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, ChinaBackground: 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. Methods: 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, in vitro siRNA knockdown experiments were carried out to assess PNP’s influence on MIBC cell proliferation. Results: 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, P < .05; GSE48075: HR > 1.5, P = .07; GSE169455: HR > 2.8, P < .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. Conclusion: This study underscores PNP’s role as a promising biomarker and therapeutic target in MIBC.https://doi.org/10.1177/11795549251359145 |
| spellingShingle | Yanfei Chen Peiyi Xian Jianming Lu Le Zhang Chao Cai Weide Zhong Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer Clinical Medicine Insights: Oncology |
| title | Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer |
| title_full | Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer |
| title_fullStr | Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer |
| title_full_unstemmed | Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer |
| title_short | Purine Nucleoside Phosphorylase (PNP) as a Biomarker and Therapeutic Target in Muscle-Invasive Bladder Cancer |
| title_sort | purine nucleoside phosphorylase pnp as a biomarker and therapeutic target in muscle invasive bladder cancer |
| url | https://doi.org/10.1177/11795549251359145 |
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