title: Abnormal DNA-PKcs and Ku 70/80 expression may promote malignant pathological processes in gastric carcinoma.
abstract: OBJECTIVE
  To determine the expression of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and the Ku70/Ku80 heterodimer (Ku 70/80) in gastric carcinoma.
  
  
  METHODS
  Gastric biopsies were obtained from 146 gastric carcinoma patients [Helicobacter pylori (H. pylori)-negative: 89 and H. pylori-positive: 57] and 34 from normal subjects (H. pylori-negative: 16 and H. pylori-positive: 18) via surgery and endoscopic detection from April 2011 to August 2012 at the First Affiliated Hospital of Nanchang University. Pathological diagnosis and classification were made according to the criteria of the World Health Organization and the updated Sydney system. An ''in-house'' rapid urease test and modified Giemsa staining were employed to detect H. pylori infection. The expression of DNA-PKcs and the Ku 70/80 protein was detected by immunohistochemistry.
  
  
  RESULTS
  Overall, the positive rates of both DNA-PKcs and Ku 70/80 were significantly increased in gastric cancer (χ(2) = 133.04, P < 0.001 for DNA-PKcs and χ(2) = 13.06, P < 0.01 for Ku) compared with normal gastric mucosa. There was hardly any detectable expression of DNA-PKcs in normal gastric mucosa, and the positive rate of DNA-PKcs protein expression in patients with a normal gastric mucosa was 0% (0/34), whereas the rate in gastric cancer (GC) was 93.8% (137/146). The difference between the two groups was statistically significant. Additionally, the positive rate of Ku 70/80 was 79.4% (27/34) in normal gastric mucosa and 96.6% (141/146) in gastric cancer. The DNA-PKcs protein level was significantly increased in gastric cancer (Mann-Whitney U = 39.00, P < 0.001), compared with normal gastric mucosa. In addition, there was a significant difference in the expression of Ku 70/80 (Mann-Whitney U = 1117.00, P < 0.001) between gastric cancer and normal gastric mucosa. There was also a significant difference in Ku70/80 protein expression between GC patients with and without H. pylori infection (P < 0.05). Spearman analysis showed a negative correlation between tumor differentiation and DNA-PKcs expression (r = -0.447, P < 0.05). Moreover, Ku70/80 expression was negatively correlated with both clinical stage (r = -0.189, P < 0.05) and H. pylori colonization (r = -0.168, P < 0.05).
  
  
  CONCLUSIONS
  Overall, this research demonstrated that enhanced DNA-PKcs and Ku 70/80 expression may be closely associated with gastric carcinoma.
authors.affiliation: Wei Li, Chuan Xie, Zhen Yang, Jiang Chen, Nong-Hua Lu, Department of Gastroenterology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Chuan
authors.initials: C
authors.lastname: Xie
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Jiang
authors.initials: J
authors.lastname: Chen
authors.forename: Nong-Hua
authors.initials: NH
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002277:Carcinoma / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D051747:DNA-Activated Protein Kinase / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D016481:Helicobacter Infections / Q000150:complications / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology
chemical_list: D034961:Antigens, Nuclear; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen
keywords: Catalytic subunit of the DNA-dependent protein kinase; Gastric carcinoma; Helicobacter pylori; Immunohistochemistry; Ku70/Ku80 heterodimer