A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients
Abstract Ubiquitin-specific proteases (USPs) are closely related to protein fate and cellular processes through various molecular signalling pathways, including DNA damage repair, p53, and transforming growth factor-β (TGF-β) pathways. In recent years, increasing evidence has revealed the pivotal ro...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12882-023-03215-0 |
| _version_ | 1797811647986794496 |
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| author | Renjie Wang Yang Liu Jingxian Li Yubao Zhao Rui An Zhifang Ma |
| author_facet | Renjie Wang Yang Liu Jingxian Li Yubao Zhao Rui An Zhifang Ma |
| author_sort | Renjie Wang |
| collection | DOAJ |
| description | Abstract Ubiquitin-specific proteases (USPs) are closely related to protein fate and cellular processes through various molecular signalling pathways, including DNA damage repair, p53, and transforming growth factor-β (TGF-β) pathways. In recent years, increasing evidence has revealed the pivotal role of ubiquitination in tumorigenesis of KIRC. However, USPs' molecular mechanism and clinical relevance in kidney cancer still need further exploration. Our study first determined prognosis-related ubiquitin-specific proteases (PRUSPs) in KIRC. We found these genes co-expressed with each other and might regulate different substrates. Based on the USPs' expression, the PRUSPs risk signature was constructed to predict the survival probability of KIRC patients. The patients in high-PRUSPs-risk group showed a low survival rate. ROC and calibration curve indicated a discriminate capacity of the signature, and uni-/multi-variate Cox regression analysis revealed that the PRUSPs score is an independent prognostic factor. In different KIRC clinical subgroups and external validation cohorts (including E-MTAB-1980 and TCGA-KIRP cohorts), the PRUSPs risk signature showed strong robustness and practicability. Further analysis found that high-risk group showed activation of immune-related pathways and high PD-1/CTLA4 expression, revealing that high-risk patients might be sensitive to immunotherapy. In summary, we constructed the USPs risk signature to predict kidney cancer prognosis, which provided the theoretical foundation for further clinical or pre-clinical experiments. |
| first_indexed | 2024-03-13T07:25:45Z |
| format | Article |
| id | doaj.art-c95f81c172cf43a6ade71074463d1eca |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-03-13T07:25:45Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-c95f81c172cf43a6ade71074463d1eca2023-06-04T11:23:26ZengBMCBMC Nephrology1471-23692023-05-0124111310.1186/s12882-023-03215-0A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patientsRenjie Wang0Yang Liu1Jingxian Li2Yubao Zhao3Rui An4Zhifang Ma5Department of Urology, Sixth Hospital of Shanxi Medical University, General Hospital of TiscoThe Second Hospital of Tianjin Medical UniversityThe Second Hospital of Tianjin Medical UniversityDepartment of Urology, Sixth Hospital of Shanxi Medical University, General Hospital of TiscoDepartment of Urology, Sixth Hospital of Shanxi Medical University, General Hospital of TiscoDepartment of Urology, First Hospital of Shanxi Medical UniversityAbstract Ubiquitin-specific proteases (USPs) are closely related to protein fate and cellular processes through various molecular signalling pathways, including DNA damage repair, p53, and transforming growth factor-β (TGF-β) pathways. In recent years, increasing evidence has revealed the pivotal role of ubiquitination in tumorigenesis of KIRC. However, USPs' molecular mechanism and clinical relevance in kidney cancer still need further exploration. Our study first determined prognosis-related ubiquitin-specific proteases (PRUSPs) in KIRC. We found these genes co-expressed with each other and might regulate different substrates. Based on the USPs' expression, the PRUSPs risk signature was constructed to predict the survival probability of KIRC patients. The patients in high-PRUSPs-risk group showed a low survival rate. ROC and calibration curve indicated a discriminate capacity of the signature, and uni-/multi-variate Cox regression analysis revealed that the PRUSPs score is an independent prognostic factor. In different KIRC clinical subgroups and external validation cohorts (including E-MTAB-1980 and TCGA-KIRP cohorts), the PRUSPs risk signature showed strong robustness and practicability. Further analysis found that high-risk group showed activation of immune-related pathways and high PD-1/CTLA4 expression, revealing that high-risk patients might be sensitive to immunotherapy. In summary, we constructed the USPs risk signature to predict kidney cancer prognosis, which provided the theoretical foundation for further clinical or pre-clinical experiments.https://doi.org/10.1186/s12882-023-03215-0USPsKidney cancerPrognostic predictionTargeted therapy |
| spellingShingle | Renjie Wang Yang Liu Jingxian Li Yubao Zhao Rui An Zhifang Ma A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients BMC Nephrology USPs Kidney cancer Prognostic prediction Targeted therapy |
| title | A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients |
| title_full | A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients |
| title_fullStr | A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients |
| title_full_unstemmed | A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients |
| title_short | A risk signature of ubiquitin-specific protease family predict the prognosis and therapy of kidney cancer patients |
| title_sort | risk signature of ubiquitin specific protease family predict the prognosis and therapy of kidney cancer patients |
| topic | USPs Kidney cancer Prognostic prediction Targeted therapy |
| url | https://doi.org/10.1186/s12882-023-03215-0 |
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