Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival
Abstract Background Cholesterol metabolism is essential for the development and progression of prostate cancer (PCa). Our previous study provided a new insight of cholesterol metabolism in the systematic management of PCa. However, the comprehensive role of cholesterol metabolism in PCa remains uncl...
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| Format: | Article |
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Springer
2024-12-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-024-01658-x |
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| author | Jian-Xuan Sun Ye An Meng-Yao Xu Si-Yang Ma Chen-Qian Liu Jin-Zhou Xu Qi-Dong Xia Shao-Gang Wang |
| author_facet | Jian-Xuan Sun Ye An Meng-Yao Xu Si-Yang Ma Chen-Qian Liu Jin-Zhou Xu Qi-Dong Xia Shao-Gang Wang |
| author_sort | Jian-Xuan Sun |
| collection | DOAJ |
| description | Abstract Background Cholesterol metabolism is essential for the development and progression of prostate cancer (PCa). Our previous study provided a new insight of cholesterol metabolism in the systematic management of PCa. However, the comprehensive role of cholesterol metabolism in PCa remains unclear. Methods Using the cholesterol metabolism related genes (CMRGs) downloaded from the MSigDB database, and gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we constructed a cholesterol risk index by the least absolute shrinkage and selection operator (LASSO) model, and correlated the risk index with prognosis, tumor mutation burden (TMB), tumor microenvironment (TME) infiltration and response to chemotherapy and immunotherapy. RT-qPCR, western blot, immunohistochemistry, cell proliferation assays by CCK-8 and EdU assays, and cell apoptosis assays by flow cytometry analysis were also performed. Results We found PCa was tightly correlated with the cholesterol metabolism pathways. The cholesterol risk index was an excellent and independent predictor of prognosis for PCa. A nomogram involving the risk index and other clinical factors (age, T stage) was established to explore the clinical value of risk index. We found high-risk index group was associated with worse prognosis, higher TMB, lower infiltration level of CD8+ T cells and a worse response to chemotherapy and immunotherapy. RT-qPCR, western blot and immunohistochemical staining validated the expression level of important CMRGs in PCa. In vitro experiments revealed downregulation of cholesterol metabolism could inhibit the proliferation of PCa cells and promoted their apoptosis. Conclusions We demonstrated the comprehensive role of cholesterol metabolism in PCa. Using the risk index, we could predict the prognosis, TME infiltration and response to chemotherapy/immunotherapy of PCa. Better understanding and evaluating the cholesterol metabolism could aid in precision medicine and promoting prognosis of PCa. |
| format | Article |
| id | doaj-art-fd14d44281a64d2b9d4a964880b60cfd |
| institution | DOAJ |
| issn | 2730-6011 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-fd14d44281a64d2b9d4a964880b60cfd2025-08-20T02:39:41ZengSpringerDiscover Oncology2730-60112024-12-0115112410.1007/s12672-024-01658-xAnalysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survivalJian-Xuan Sun0Ye An1Meng-Yao Xu2Si-Yang Ma3Chen-Qian Liu4Jin-Zhou Xu5Qi-Dong Xia6Shao-Gang Wang7Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background Cholesterol metabolism is essential for the development and progression of prostate cancer (PCa). Our previous study provided a new insight of cholesterol metabolism in the systematic management of PCa. However, the comprehensive role of cholesterol metabolism in PCa remains unclear. Methods Using the cholesterol metabolism related genes (CMRGs) downloaded from the MSigDB database, and gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we constructed a cholesterol risk index by the least absolute shrinkage and selection operator (LASSO) model, and correlated the risk index with prognosis, tumor mutation burden (TMB), tumor microenvironment (TME) infiltration and response to chemotherapy and immunotherapy. RT-qPCR, western blot, immunohistochemistry, cell proliferation assays by CCK-8 and EdU assays, and cell apoptosis assays by flow cytometry analysis were also performed. Results We found PCa was tightly correlated with the cholesterol metabolism pathways. The cholesterol risk index was an excellent and independent predictor of prognosis for PCa. A nomogram involving the risk index and other clinical factors (age, T stage) was established to explore the clinical value of risk index. We found high-risk index group was associated with worse prognosis, higher TMB, lower infiltration level of CD8+ T cells and a worse response to chemotherapy and immunotherapy. RT-qPCR, western blot and immunohistochemical staining validated the expression level of important CMRGs in PCa. In vitro experiments revealed downregulation of cholesterol metabolism could inhibit the proliferation of PCa cells and promoted their apoptosis. Conclusions We demonstrated the comprehensive role of cholesterol metabolism in PCa. Using the risk index, we could predict the prognosis, TME infiltration and response to chemotherapy/immunotherapy of PCa. Better understanding and evaluating the cholesterol metabolism could aid in precision medicine and promoting prognosis of PCa.https://doi.org/10.1007/s12672-024-01658-xCholesterol metabolismTumor microenvironmentTumor mutation burdenProstate cancerChemotherapyImmunotherapy |
| spellingShingle | Jian-Xuan Sun Ye An Meng-Yao Xu Si-Yang Ma Chen-Qian Liu Jin-Zhou Xu Qi-Dong Xia Shao-Gang Wang Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival Discover Oncology Cholesterol metabolism Tumor microenvironment Tumor mutation burden Prostate cancer Chemotherapy Immunotherapy |
| title | Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival |
| title_full | Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival |
| title_fullStr | Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival |
| title_full_unstemmed | Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival |
| title_short | Analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival |
| title_sort | analysis of transcriptomic data reveals the landscape of cholesterol metabolism in prostate cancer and impact of related signature on survival |
| topic | Cholesterol metabolism Tumor microenvironment Tumor mutation burden Prostate cancer Chemotherapy Immunotherapy |
| url | https://doi.org/10.1007/s12672-024-01658-x |
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