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Association of DDR pathway proteins and breast cancer risk in a Pakistani population

Azhar Mehmood1,2, Ishrat Mahjabeen1, Simon Reed2

  • 1Cancer Genetics & Epigenetics Group, Department of Bioscience, COMSATS University Islamabad, Islamabad, Pakistan.

Future Oncology (London, England)
|October 30, 2025
PubMed
Abstract

Insights

This study found that decreased expression of ATM, CHEK1, and CHEK2 proteins in breast tumors indicates aggressive cancer. These DNA Damage Response (DDR) proteins show promise as diagnostic and prognostic markers for breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer is a heterogeneous disease with variable treatment responses.
  • Dysregulation of DNA Damage Response (DDR) pathway genes contributes to cancer risk, progression, and metastasis.

Purpose of the Study:

  • To investigate the expression patterns of ATM, CHEK1, and CHEK2 proteins in breast cancer.
  • To evaluate the diagnostic and prognostic potential of these DDR proteins.

Main Methods:

  • Immunohistochemistry-based expression profiling of ATM, CHEK1, and CHEK2 proteins.
  • Analysis of 102 breast cancer tissues and adjacent control tissues.

Main Results:

  • Downregulated expression of ATM, CHEK1, and CHEK2 proteins was observed in breast tumor tissues compared to controls.
  • Downregulated protein expression correlated with aggressive breast cancer phenotypes and increased tumor burden.
  • ATM, CHEK1, and CHEK2 proteins demonstrated significant diagnostic potential with high area under the curve values.

Conclusions:

  • Dysregulated expression of ATM, CHEK1, and CHEK2 is associated with poor survival outcomes in breast cancer patients.
  • These proteins may serve as effective diagnostic and prognostic markers for early detection and treatment.
Keywords:
Breast cancerDDR pathway genesIHCdiagnosissurvival analysis

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