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Tumor Biology

, Volume 35, Issue 6, pp 5971–5983 | Cite as

Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma

  • Ishrat Mahjabeen
  • Kashif Ali
  • Xiaofeng Zhou
  • Mahmood Akhtar Kayani
Research Article

Abstract

Defects in the DNA damage repair pathway contribute to cancer. The major pathway for oxidative DNA damage repair is base excision repair (BER). Although BER pathway genes (OGG1, APEX1 and XRCC1) have been investigated in a number of cancers, our knowledge on the prognostic significance of these genes and their role in head and neck squamous cell carcinoma is limited. Protein levels of OGG1, APEX1 and XRCC1 and a proliferation marker, Ki-67, were examined by immunohistochemical analysis, in a cohort of 50 HNSCC patients. Significant downregulation of OGG1 (p < 0.04) and XRCC1 (p < 0.05) was observed in poorly differentiated HNSCC compared to mod–well-differentiated cases. Significant upregulation of APEX1 (p < 0.05) and Ki-67 (p < 0.05) was observed in poorly differentiated HNSCC compared to mod-well-differentiated cases. Significant correlation was observed between XRCC1 and OGG1 (r = 0.33, p < 0.02). Inverse correlations were observed between OGG1 and Ki-67 (r = −0.377, p < 0.005), between APEX1 and XRCC1 (r = −0.435, p < 0.002) and between OGG1 and APEX1 (r = −0.34, p < 0.02) in HNSCC. To confirm our observations, we examined BER pathway genes and a proliferation marker, Ki-67, expression at the mRNA level on 50 head and neck squamous cell carcinoma (HNSCC) and 50 normal control samples by quantitative real-time polymerase chain reaction. Significant downregulation was observed in case of OGG1 (p < 0.04) and XRCC1 (p < 0.02), while significant upregulation was observed in case of APEX1 (p < 0.01) and Ki-67 (p < 0.03) in HNSCC tissue samples compared to controls. Our data suggested that deregulation of base excision repair pathway genes, such as OGG1, APEX1 and XRCC1, combined with overexpression of Ki-67, a marker for excessive proliferation, may contribute to progression of HNSCC in Pakistani population.

Keywords

HNSCC BER pathway gene Proliferation marker Immunohistochemistry 

Notes

Acknowledgments

This study was supported by grants from the Higher Education Commission (HEC) of Pakistan, the COMSATS Institute of Information Technology (CIIT), Islamabad, and the NIH PHS grant (CA139596).

Conflicts of interests

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ishrat Mahjabeen
    • 1
    • 2
  • Kashif Ali
    • 1
  • Xiaofeng Zhou
    • 2
    • 3
  • Mahmood Akhtar Kayani
    • 1
  1. 1.Cancer Genetics Lab, Department of BiosciencesCOMSATS Institute of Information and TechnologyIslamabadPakistan
  2. 2.Center for Molecular Biology of Oral Diseases, College of DentistryUniversity of Illinois at ChicagoChicagoUSA
  3. 3.Department of Periodontics, College of Dentistry, Graduate College, UIC Cancer CenterUniversity of Illinois at ChicagoChicagoUSA

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