Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer
Background: Increasing evidences show a clinical significance in the interaction between hypoxia and prostate cancer. However, reliable prognostic signatures based on hypoxia have not been established yet.Methods: We screened hypoxia-related gene modules by weighted gene co-expression network analys...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.922074/full |
| _version_ | 1828438098658197504 |
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| author | Minhua Chen Zhang Chen Zongbin Lin Xiang Ding Tianyu Liang |
| author_facet | Minhua Chen Zhang Chen Zongbin Lin Xiang Ding Tianyu Liang |
| author_sort | Minhua Chen |
| collection | DOAJ |
| description | Background: Increasing evidences show a clinical significance in the interaction between hypoxia and prostate cancer. However, reliable prognostic signatures based on hypoxia have not been established yet.Methods: We screened hypoxia-related gene modules by weighted gene co-expression network analysis (WGCNA) and established a hypoxia-related prognostic risk score (HPRS) model by univariate Cox and LASSO-Cox analyses. In addition, enriched pathways, genomic mutations, and tumor-infiltrating immune cells in HPRS subgroups were analyzed and compared. HPRS was also estimated to predict immune checkpoint blockade (ICB) therapy response.Results: A hypoxia-related 22-gene prognostic model was established. Furthermore, three independent validation cohorts showed moderate performance in predicting biochemical recurrence-free (BCR-free) survival. HPRS could be a useful tool in selecting patients who can benefit from ICB therapy. The CIBERSORT results in our study demonstrated that hypoxia might act on multiple T cells, activated NK cells, and macrophages M1 in various ways, suggesting that hypoxia might exert its anti-tumor effects by suppressing T cells and NK cells.Conclusion: Hypoxia plays an important role in the progression of prostate cancer. The hypoxia-derived signatures are promising biomarkers to predict biochemical recurrence-free survival and ICB therapy responses in patients with prostate cancer. |
| first_indexed | 2024-12-10T19:58:11Z |
| format | Article |
| id | doaj.art-a841218c67ff4ead85ac4aaec7e9dfb8 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-10T19:58:11Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-a841218c67ff4ead85ac4aaec7e9dfb82022-12-22T01:35:36ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.922074922074Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancerMinhua Chen0Zhang Chen1Zongbin Lin2Xiang Ding3Tianyu Liang4Emergency & Intensive Care Unit Center, Department of Intensive Care Unit, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaEmergency & Intensive Care Unit Center, Department of Intensive Care Unit, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, ChinaDepartment of Urology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaEmergency & Intensive Care Unit Center, Department of Intensive Care Unit, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, ChinaBackground: Increasing evidences show a clinical significance in the interaction between hypoxia and prostate cancer. However, reliable prognostic signatures based on hypoxia have not been established yet.Methods: We screened hypoxia-related gene modules by weighted gene co-expression network analysis (WGCNA) and established a hypoxia-related prognostic risk score (HPRS) model by univariate Cox and LASSO-Cox analyses. In addition, enriched pathways, genomic mutations, and tumor-infiltrating immune cells in HPRS subgroups were analyzed and compared. HPRS was also estimated to predict immune checkpoint blockade (ICB) therapy response.Results: A hypoxia-related 22-gene prognostic model was established. Furthermore, three independent validation cohorts showed moderate performance in predicting biochemical recurrence-free (BCR-free) survival. HPRS could be a useful tool in selecting patients who can benefit from ICB therapy. The CIBERSORT results in our study demonstrated that hypoxia might act on multiple T cells, activated NK cells, and macrophages M1 in various ways, suggesting that hypoxia might exert its anti-tumor effects by suppressing T cells and NK cells.Conclusion: Hypoxia plays an important role in the progression of prostate cancer. The hypoxia-derived signatures are promising biomarkers to predict biochemical recurrence-free survival and ICB therapy responses in patients with prostate cancer.https://www.frontiersin.org/articles/10.3389/fgene.2022.922074/fullprostate cancerhypoxiaimmune checkpoint blockadeprognosticoutcome |
| spellingShingle | Minhua Chen Zhang Chen Zongbin Lin Xiang Ding Tianyu Liang Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer Frontiers in Genetics prostate cancer hypoxia immune checkpoint blockade prognostic outcome |
| title | Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer |
| title_full | Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer |
| title_fullStr | Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer |
| title_full_unstemmed | Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer |
| title_short | Utilization of hypoxia-derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer |
| title_sort | utilization of hypoxia derived gene signatures to predict clinical outcomes and immune checkpoint blockade therapy responses in prostate cancer |
| topic | prostate cancer hypoxia immune checkpoint blockade prognostic outcome |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.922074/full |
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