Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma
Abstract Pancreatic adenocarcinoma (PAAD) is a highly aggressive and lethal malignancy, characterized by late diagnosis, rapid progression, and poor response to conventional therapies. Altered nucleotide metabolism has recently been recognized as a critical driver of tumorigenesis, impacting cellula...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-10098-8 |
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| author | Chaojie Zhai Jiarong Ye Ziyang Zhou Hongliang Luo Xiaoyan Li Jipeng Liu Xinchi Zhou Zuao Wang Xu Zhang Wen Zeng Leifeng Chen Fan Zhou |
| author_facet | Chaojie Zhai Jiarong Ye Ziyang Zhou Hongliang Luo Xiaoyan Li Jipeng Liu Xinchi Zhou Zuao Wang Xu Zhang Wen Zeng Leifeng Chen Fan Zhou |
| author_sort | Chaojie Zhai |
| collection | DOAJ |
| description | Abstract Pancreatic adenocarcinoma (PAAD) is a highly aggressive and lethal malignancy, characterized by late diagnosis, rapid progression, and poor response to conventional therapies. Altered nucleotide metabolism has recently been recognized as a critical driver of tumorigenesis, impacting cellular proliferation, invasion, and immune evasion. However, the role of specific metabolic enzymes, such as NT5M (cytosolic 5′-nucleotidase, mitochondrial), in PAAD remains poorly understood. In this study, we employed an integrated approach combining comprehensive bioinformatics analysis with systematic in vitro functional assays to investigate the multifaceted roles of NT5M in PAAD. Our investigation focused on three key aspects: (1) establishing NT5M as a novel prognostic biomarker, with lower expression levels significantly correlating with poor clinical outcomes; (2) characterizing the association between NT5M expression and tumor microenvironment (TME) features; and (3) elucidating the mechanistic role of NT5M in immune regulation within PAAD. Importantly, we discovered that NT5M downregulation is associated with increased CXCL8 expression and subsequent PD-L1 upregulation, thereby reversing immune evasion in pancreatic cancer. These findings establish NT5M as both a valuable prognostic indicator for tumor progression and a promising therapeutic target for PAAD. The identification of these interconnected pathways provides a novel strategy for enhancing the efficacy of immune checkpoint blockade therapies, potentially overcoming the current limitations in pancreatic cancer immunotherapy. |
| format | Article |
| id | doaj-art-a0211dace3634f32b572d1c93a523536 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-a0211dace3634f32b572d1c93a5235362025-08-20T03:45:59ZengNature PortfolioScientific Reports2045-23222025-07-0115111910.1038/s41598-025-10098-8Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinomaChaojie Zhai0Jiarong Ye1Ziyang Zhou2Hongliang Luo3Xiaoyan Li4Jipeng Liu5Xinchi Zhou6Zuao Wang7Xu Zhang8Wen Zeng9Leifeng Chen10Fan Zhou11Department of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityBiobank Center, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityDepartment of General Surgery, The Second Affiliated Hospital of Nanchang UniversityAbstract Pancreatic adenocarcinoma (PAAD) is a highly aggressive and lethal malignancy, characterized by late diagnosis, rapid progression, and poor response to conventional therapies. Altered nucleotide metabolism has recently been recognized as a critical driver of tumorigenesis, impacting cellular proliferation, invasion, and immune evasion. However, the role of specific metabolic enzymes, such as NT5M (cytosolic 5′-nucleotidase, mitochondrial), in PAAD remains poorly understood. In this study, we employed an integrated approach combining comprehensive bioinformatics analysis with systematic in vitro functional assays to investigate the multifaceted roles of NT5M in PAAD. Our investigation focused on three key aspects: (1) establishing NT5M as a novel prognostic biomarker, with lower expression levels significantly correlating with poor clinical outcomes; (2) characterizing the association between NT5M expression and tumor microenvironment (TME) features; and (3) elucidating the mechanistic role of NT5M in immune regulation within PAAD. Importantly, we discovered that NT5M downregulation is associated with increased CXCL8 expression and subsequent PD-L1 upregulation, thereby reversing immune evasion in pancreatic cancer. These findings establish NT5M as both a valuable prognostic indicator for tumor progression and a promising therapeutic target for PAAD. The identification of these interconnected pathways provides a novel strategy for enhancing the efficacy of immune checkpoint blockade therapies, potentially overcoming the current limitations in pancreatic cancer immunotherapy.https://doi.org/10.1038/s41598-025-10098-8Pancreatic adenocarcinoma (PAAD)NT5MCXCL8PD-L1Immune |
| spellingShingle | Chaojie Zhai Jiarong Ye Ziyang Zhou Hongliang Luo Xiaoyan Li Jipeng Liu Xinchi Zhou Zuao Wang Xu Zhang Wen Zeng Leifeng Chen Fan Zhou Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma Scientific Reports Pancreatic adenocarcinoma (PAAD) NT5M CXCL8 PD-L1 Immune |
| title | Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma |
| title_full | Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma |
| title_fullStr | Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma |
| title_full_unstemmed | Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma |
| title_short | Bioinformatics analysis identifies NT5M modulates immune evasion through PD-L1 via CXCL8 in pancreatic adenocarcinoma |
| title_sort | bioinformatics analysis identifies nt5m modulates immune evasion through pd l1 via cxcl8 in pancreatic adenocarcinoma |
| topic | Pancreatic adenocarcinoma (PAAD) NT5M CXCL8 PD-L1 Immune |
| url | https://doi.org/10.1038/s41598-025-10098-8 |
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