Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer
Abstract Ubiquitin-Specific Protease 39 (USP39) has been implicated in numerous malignancies, however, its pathogenic mechanisms and impact on the tumor immune microenvironment (TIME) remain incompletely characterized. Based on The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx)...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12885-025-14096-x |
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| author | Jiahui Yuan Beibei Xu Yongcheng Su Pingping Zhang Xianbin Zhang Peng Gong |
| author_facet | Jiahui Yuan Beibei Xu Yongcheng Su Pingping Zhang Xianbin Zhang Peng Gong |
| author_sort | Jiahui Yuan |
| collection | DOAJ |
| description | Abstract Ubiquitin-Specific Protease 39 (USP39) has been implicated in numerous malignancies, however, its pathogenic mechanisms and impact on the tumor immune microenvironment (TIME) remain incompletely characterized. Based on The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we investigated the diagnostic and prognostic values of USP39 across various cancer types. Additionally, we examined the correlation between USP39 expression and immune-related gene signature, immune cell infiltration pattern, tumor microsatellite instability (MSI), and tumor mutation burden (TMB). This study specifically focused on exploring the clinical relevance and molecular functions of USP39 in pancreatic adenocarcinoma (PAAD), with particularly emphasis on its role in shaping the TIME and modulating responses to immunotherapy. The results demonstrated that evaluated USP39 expression significantly correlated with advanced tumor stage and unfavorable clinical outcomes across multiple cancer types, most notably in PAAD. Functional enrichment analysis indicated that USP39 potentially promotes tumor progression through multiple oncogenic signaling cascades. In vitro experimental validation confirmed that USP39 knockdown inhibited migration and proliferation of pancreatic cancer cells while inducing apoptosis. Additionally, we identified significant positive correlations between USP39 expression and immune checkpoint molecules, particularly prominent in PAAD. Furthermore, we observed associations between USP39 expression and TMB in 16 cancer types and MSI in 11 cancer types, suggesting that heightened USP39 expression may enhance responsiveness to immunotherapeutic interventions. Collectively, our findings establish USP39 as a valuable immune-related biomarker with both diagnostic and prognostic utility across multiple cancer types, especially PAAD, underscoring its potential as a promising therapeutic target for cancer immunotherapy. Clinical trial number Not applicable. |
| format | Article |
| id | doaj-art-c9b58fc70a0c4429a3eb7082ec4d63da |
| institution | OA Journals |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | BMC Cancer |
| spelling | doaj-art-c9b58fc70a0c4429a3eb7082ec4d63da2025-08-20T02:20:25ZengBMCBMC Cancer1471-24072025-04-0125111810.1186/s12885-025-14096-xIdentification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancerJiahui Yuan0Beibei Xu1Yongcheng Su2Pingping Zhang3Xianbin Zhang4Peng Gong5Department of General Surgery, Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen UniversityCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of SciencesXiamen Key Laboratory for Tumor Metastasis, Cancer Research School of Medicine, Xiamen UniversityDepartment of Gastroenterology, Changhai Hospital, Naval Medical UniversityDepartment of General Surgery, Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen UniversityDepartment of General Surgery, Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen UniversityAbstract Ubiquitin-Specific Protease 39 (USP39) has been implicated in numerous malignancies, however, its pathogenic mechanisms and impact on the tumor immune microenvironment (TIME) remain incompletely characterized. Based on The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we investigated the diagnostic and prognostic values of USP39 across various cancer types. Additionally, we examined the correlation between USP39 expression and immune-related gene signature, immune cell infiltration pattern, tumor microsatellite instability (MSI), and tumor mutation burden (TMB). This study specifically focused on exploring the clinical relevance and molecular functions of USP39 in pancreatic adenocarcinoma (PAAD), with particularly emphasis on its role in shaping the TIME and modulating responses to immunotherapy. The results demonstrated that evaluated USP39 expression significantly correlated with advanced tumor stage and unfavorable clinical outcomes across multiple cancer types, most notably in PAAD. Functional enrichment analysis indicated that USP39 potentially promotes tumor progression through multiple oncogenic signaling cascades. In vitro experimental validation confirmed that USP39 knockdown inhibited migration and proliferation of pancreatic cancer cells while inducing apoptosis. Additionally, we identified significant positive correlations between USP39 expression and immune checkpoint molecules, particularly prominent in PAAD. Furthermore, we observed associations between USP39 expression and TMB in 16 cancer types and MSI in 11 cancer types, suggesting that heightened USP39 expression may enhance responsiveness to immunotherapeutic interventions. Collectively, our findings establish USP39 as a valuable immune-related biomarker with both diagnostic and prognostic utility across multiple cancer types, especially PAAD, underscoring its potential as a promising therapeutic target for cancer immunotherapy. Clinical trial number Not applicable.https://doi.org/10.1186/s12885-025-14096-xUSP39Pancreatic cancerPrognosisTumor microenvironmentImmunotherapy |
| spellingShingle | Jiahui Yuan Beibei Xu Yongcheng Su Pingping Zhang Xianbin Zhang Peng Gong Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer BMC Cancer USP39 Pancreatic cancer Prognosis Tumor microenvironment Immunotherapy |
| title | Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer |
| title_full | Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer |
| title_fullStr | Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer |
| title_full_unstemmed | Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer |
| title_short | Identification of USP39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer |
| title_sort | identification of usp39 as a prognostic and predictive biomarker for determining the response to immunotherapy in pancreatic cancer |
| topic | USP39 Pancreatic cancer Prognosis Tumor microenvironment Immunotherapy |
| url | https://doi.org/10.1186/s12885-025-14096-x |
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