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Updated: May 2, 2026
Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell
Ishrat Mahjabeen1, Kashif Ali, Xiaofeng Zhou
1Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information and Technology, Park Road Chakshazad, Islamabad, Pakistan.
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.
Insights
Defects in DNA repair, specifically base excision repair (BER) genes OGG1, APEX1, and XRCC1, are linked to head and neck squamous cell carcinoma (HNSCC) progression. Deregulation of these BER genes and overexpression of the proliferation marker Ki-67 correlate with HNSCC advancement.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Defects in DNA damage repair pathways are implicated in cancer development.
- The base excision repair (BER) pathway is crucial for repairing oxidative DNA damage.
- The prognostic significance of BER genes (OGG1, APEX1, XRCC1) in head and neck squamous cell carcinoma (HNSCC) is not well understood.
Purpose of the Study:
- To investigate the prognostic significance of BER pathway genes OGG1, APEX1, and XRCC1 in HNSCC.
- To evaluate the expression levels of these BER genes and the proliferation marker Ki-67 in HNSCC tissues.
- To determine the association between BER gene expression, Ki-67, and HNSCC differentiation and progression.
Main Methods:
- Immunohistochemical analysis of OGG1, APEX1, XRCC1, and Ki-67 protein levels in 50 HNSCC patient samples.
- Quantitative real-time polymerase chain reaction (qRT-PCR) to assess mRNA expression of BER genes and Ki-67 in 50 HNSCC and 50 normal control samples.
- Statistical analysis to correlate gene expression with clinicopathological features and patient outcomes.
Main Results:
- Downregulation of OGG1 and XRCC1 was observed in poorly differentiated HNSCC compared to well-differentiated cases.
- Upregulation of APEX1 and Ki-67 was found in poorly differentiated HNSCC.
- mRNA analysis confirmed downregulation of OGG1 and XRCC1, and upregulation of APEX1 and Ki-67 in HNSCC tissues compared to controls.
- Significant correlations were found between OGG1, XRCC1, APEX1, and Ki-67, suggesting pathway interplay.
Conclusions:
- Deregulation of BER pathway genes (OGG1, APEX1, XRCC1) is associated with HNSCC progression.
- Overexpression of the proliferation marker Ki-67 correlates with HNSCC advancement.
- These molecular alterations may contribute to HNSCC development and progression, particularly in the Pakistani population.
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