Mehmood, Azhar, Mahjabeen, Ishrat, Reed, Simon  ORCID: https://orcid.org/0000-0002-4711-0560, Errington, Rachel J. ORCID: https://orcid.org/0000-0002-8016-4376, Umar, Muhammad, Pervaiz, Farrah and Kayani, Mahmood A.
2025.
Association of DDR pathway proteins and breast cancer risk in a Pakistani population.
Future Oncology
10.1080/14796694.2025.2581508
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Abstract
Introduction Breast cancer, due to its heterogeneous nature and variable response to current systemic treatment, can be a great concern. Deregulation of the DNA Damage Response (DDR) pathway genes due to mutation and expression increases cancer risk, progression, and metastasis. The current study was designed to check the expression deregulation patterns of the selected DDR pathway genes (ATM, CHEK1, and CHEK2) at the protein level. Material & method Immunohistochemistry-based expression profiling was conducted in 102 histopathological confirmed breast cancer-diagnosed tissues and their adjacent uninvolved control tissues. Results Downregulated expression of the selected DDR pathway (ATM, CHEK1, and CHEK2) proteins was observed in breast tumor tissues compared to control tissues. Downregulated protein expression of the DDR pathway genes (ATM, CHEK1, and CHEK2) correlates with aggressive breast cancer phenotypes and increased tumor burden. The selected proteins showed significant diagnostic potential having strong area under curve values for CHEK2 (0.828, p < 0.0001), CHEK1 (775, p < 0.0001) and ATM (0.725, < 0.0001) proteins. Conclusions Kaplan–Meier analysis showed that dysregulated expression of these three proteins leads toward poor survival outcomes, suggesting their role to be used as a better and more effective diagnostic and prognostic marker for early diagnosis and effective treatment of breast cancer patients.
| Item Type: | Article |
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| Date Type: | Published Online |
| Status: | In Press |
| Schools: | Schools > Medicine |
| Publisher: | Taylor and Francis Group |
| ISSN: | 1479-6694 |
| Date of Acceptance: | 24 October 2025 |
| Last Modified: | 11 Nov 2025 11:34 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/182318 |
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