Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair
Abstract Background P38 mitogen activated protein kinase is an intermediary signal transduction factor with context-specific roles in breast cancer. Recent mechanistic studies add to the growing consensus that P38 is a tumour suppressor, and it may represent a novel target for breast cancer treatmen...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4924-2 |
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| author | Simon J. Johnston Dena Ahmad Mohammed A. Aleskandarany Sasagu Kurozumi Chris C. Nolan Maria Diez-Rodriguez Andrew R. Green Emad A. Rakha |
| author_facet | Simon J. Johnston Dena Ahmad Mohammed A. Aleskandarany Sasagu Kurozumi Chris C. Nolan Maria Diez-Rodriguez Andrew R. Green Emad A. Rakha |
| author_sort | Simon J. Johnston |
| collection | DOAJ |
| description | Abstract Background P38 mitogen activated protein kinase is an intermediary signal transduction factor with context-specific roles in breast cancer. Recent mechanistic studies add to the growing consensus that P38 is a tumour suppressor, and it may represent a novel target for breast cancer treatment. The aim of this study is to add definitive data on the prognostic value of P38 and its link with biomarkers in primary breast cancer. Methods A large, well-characterised series of 1332 primary breast cancer patients with long-term clinical follow-up was assessed for P38 expression by immunohistochemistry. Association of clinicopathological factors and a panel of breast cancer biomarkers was determined by chi-squared test, and multivariate survival analysis was performed using Cox Proportional Hazards regression modelling. Results This study shows that nuclear P38 is co-expressed with nuclear hormone receptors (p < 0.001) and is an independent prognostic marker of good long-term clinical outcome in primary breast cancer (hazard ratio 0.796, 95% confidence interval 0.662–0.957, p = 0.015). Significant association was found between expression of P38 and markers of DNA repair including nuclear BRCA1 and RAD51, and cleaved PARP1 (all p < 0.001). Conclusions The findings support the proposed role for P38 as a tumour suppressor in breast cancer via upregulation of DNA repair proteins and provide novel hypothesis-generating information on the potential role of P38 in adjuvant therapy decision making. |
| first_indexed | 2024-12-13T12:45:47Z |
| format | Article |
| id | doaj.art-3758fe8095cf420d90a08aa95b669c9c |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-13T12:45:47Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-3758fe8095cf420d90a08aa95b669c9c2022-12-21T23:45:29ZengBMCBMC Cancer1471-24072018-10-011811910.1186/s12885-018-4924-2Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repairSimon J. Johnston0Dena Ahmad1Mohammed A. Aleskandarany2Sasagu Kurozumi3Chris C. Nolan4Maria Diez-Rodriguez5Andrew R. Green6Emad A. Rakha7Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamNottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamNottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamNottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamNottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamNottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamNottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamNottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, The University of NottinghamAbstract Background P38 mitogen activated protein kinase is an intermediary signal transduction factor with context-specific roles in breast cancer. Recent mechanistic studies add to the growing consensus that P38 is a tumour suppressor, and it may represent a novel target for breast cancer treatment. The aim of this study is to add definitive data on the prognostic value of P38 and its link with biomarkers in primary breast cancer. Methods A large, well-characterised series of 1332 primary breast cancer patients with long-term clinical follow-up was assessed for P38 expression by immunohistochemistry. Association of clinicopathological factors and a panel of breast cancer biomarkers was determined by chi-squared test, and multivariate survival analysis was performed using Cox Proportional Hazards regression modelling. Results This study shows that nuclear P38 is co-expressed with nuclear hormone receptors (p < 0.001) and is an independent prognostic marker of good long-term clinical outcome in primary breast cancer (hazard ratio 0.796, 95% confidence interval 0.662–0.957, p = 0.015). Significant association was found between expression of P38 and markers of DNA repair including nuclear BRCA1 and RAD51, and cleaved PARP1 (all p < 0.001). Conclusions The findings support the proposed role for P38 as a tumour suppressor in breast cancer via upregulation of DNA repair proteins and provide novel hypothesis-generating information on the potential role of P38 in adjuvant therapy decision making.http://link.springer.com/article/10.1186/s12885-018-4924-2Breast cancerP38MAPKOestrogen receptorAdjuvantSurvival |
| spellingShingle | Simon J. Johnston Dena Ahmad Mohammed A. Aleskandarany Sasagu Kurozumi Chris C. Nolan Maria Diez-Rodriguez Andrew R. Green Emad A. Rakha Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair BMC Cancer Breast cancer P38 MAPK Oestrogen receptor Adjuvant Survival |
| title | Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair |
| title_full | Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair |
| title_fullStr | Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair |
| title_full_unstemmed | Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair |
| title_short | Co-expression of nuclear P38 and hormone receptors is prognostic of good long-term clinical outcome in primary breast cancer and is linked to upregulation of DNA repair |
| title_sort | co expression of nuclear p38 and hormone receptors is prognostic of good long term clinical outcome in primary breast cancer and is linked to upregulation of dna repair |
| topic | Breast cancer P38 MAPK Oestrogen receptor Adjuvant Survival |
| url | http://link.springer.com/article/10.1186/s12885-018-4924-2 |
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