title: Deregulation of base excision repair gene expression and enhanced proliferation in head and neck squamous cell carcinoma.
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.
authors.affiliation: Cancer Genetics Lab, Department of Biosciences, COMSATS Institute of Information and Technology, Park Road Chakshazad, Islamabad, Pakistan.
authors.forename: Ishrat
authors.initials: I
authors.lastname: Mahjabeen
authors.forename: Kashif
authors.initials: K
authors.lastname: Ali
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhou
authors.forename: Mahmood Akhtar
authors.initials: MA
authors.lastname: Kayani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D045647:DNA Glycosylases / Q000032:analysis / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D000077195:Squamous Cell Carcinoma of Head and Neck; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase