A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancer
Abstract Background Metabolic reprogramming is a hallmark in cancer. Pyrimidine metabolism (PM), a part of nucleotide metabolism, has been shown to be associated with the progression of various cancers, and the prognostic predictive ability of pyrimidine metabolism-related genes (PMG) in breast canc...
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| Language: | English |
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BMC
2025-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06700-2 |
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| author | Han Wang Ziling Zhou Hanyi Zhong Shoutang Wang Kunwei Shen Renhong Huang Ruo Wang Zheng Wang |
| author_facet | Han Wang Ziling Zhou Hanyi Zhong Shoutang Wang Kunwei Shen Renhong Huang Ruo Wang Zheng Wang |
| author_sort | Han Wang |
| collection | DOAJ |
| description | Abstract Background Metabolic reprogramming is a hallmark in cancer. Pyrimidine metabolism (PM), a part of nucleotide metabolism, has been shown to be associated with the progression of various cancers, and the prognostic predictive ability of pyrimidine metabolism-related genes (PMG) in breast cancer has not been elucidated. This paper was designed to identify pyrimidine metabolism-related prognostic marker of breast cancer and potential targeted therapeutic options. Methods The cohort in the TCGA-BRCA dataset was used for patient information, and 108 pyrimidine metabolism-related genes were identified from the MSigDB KEGG pathways. We identified PM clusters in breast cancer and established a PM risk score model based on 10 pyrimidine metabolism-related genes. The status of immune infiltration was assessed in different groups. Further we identified the relevant hub gene and analyzed its significance for breast cancer metastasis and explored patterns of combination therapy. Results We identified three types of PM clusters in breast cancer and clarified that PM cluster C with inferior prognosis possessed activation of tumor proliferation-associated pathways. The high-risk group in PM risk score model was found to be characterized by an immunosuppressive microenvironment. The hub gene POLR2C (RNA polymerase II subunit C) was further identified and verified as a potential prognostic marker. Furthermore, targeting POLR2C in combination with anti-PD-1 and anti-angiogenic therapies demonstrated a promising tumor suppression effect, suggesting a potential therapeutic direction. Conclusions These findings provide additional insights into the link between breast cancer and PMG, offering potential strategies for breast cancer management and treatment. |
| format | Article |
| id | doaj-art-c31753dbf3f449a98c853b1de7ae8daa |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-c31753dbf3f449a98c853b1de7ae8daa2025-08-20T03:27:11ZengBMCJournal of Translational Medicine1479-58762025-06-0123111610.1186/s12967-025-06700-2A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancerHan Wang0Ziling Zhou1Hanyi Zhong2Shoutang Wang3Kunwei Shen4Renhong Huang5Ruo Wang6Zheng Wang7Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineSchool of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong KongDepartment of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Breast Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial HospitalDepartment of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background Metabolic reprogramming is a hallmark in cancer. Pyrimidine metabolism (PM), a part of nucleotide metabolism, has been shown to be associated with the progression of various cancers, and the prognostic predictive ability of pyrimidine metabolism-related genes (PMG) in breast cancer has not been elucidated. This paper was designed to identify pyrimidine metabolism-related prognostic marker of breast cancer and potential targeted therapeutic options. Methods The cohort in the TCGA-BRCA dataset was used for patient information, and 108 pyrimidine metabolism-related genes were identified from the MSigDB KEGG pathways. We identified PM clusters in breast cancer and established a PM risk score model based on 10 pyrimidine metabolism-related genes. The status of immune infiltration was assessed in different groups. Further we identified the relevant hub gene and analyzed its significance for breast cancer metastasis and explored patterns of combination therapy. Results We identified three types of PM clusters in breast cancer and clarified that PM cluster C with inferior prognosis possessed activation of tumor proliferation-associated pathways. The high-risk group in PM risk score model was found to be characterized by an immunosuppressive microenvironment. The hub gene POLR2C (RNA polymerase II subunit C) was further identified and verified as a potential prognostic marker. Furthermore, targeting POLR2C in combination with anti-PD-1 and anti-angiogenic therapies demonstrated a promising tumor suppression effect, suggesting a potential therapeutic direction. Conclusions These findings provide additional insights into the link between breast cancer and PMG, offering potential strategies for breast cancer management and treatment.https://doi.org/10.1186/s12967-025-06700-2Pyrimidine metabolismGene signatureBreast cancerPOLR2C |
| spellingShingle | Han Wang Ziling Zhou Hanyi Zhong Shoutang Wang Kunwei Shen Renhong Huang Ruo Wang Zheng Wang A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancer Journal of Translational Medicine Pyrimidine metabolism Gene signature Breast cancer POLR2C |
| title | A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancer |
| title_full | A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancer |
| title_fullStr | A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancer |
| title_full_unstemmed | A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancer |
| title_short | A pyrimidine metabolism-related gene signature for prognosis prediction and immune microenvironment description of breast cancer |
| title_sort | pyrimidine metabolism related gene signature for prognosis prediction and immune microenvironment description of breast cancer |
| topic | Pyrimidine metabolism Gene signature Breast cancer POLR2C |
| url | https://doi.org/10.1186/s12967-025-06700-2 |
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