Overexpression of Ku80 suggests poor prognosis of locally advanced esophageal squamous cell carcinoma patients

World J Surg. 2015 Jul;39(7):1773-81. doi: 10.1007/s00268-015-3023-7.

Abstract

Background: Recent studies have shown that Ku80 expression was implicated in development and progression of malignant tumors. In the present study, we analyzed for the first time the expression of Ku80 in locally advanced esophageal squamous cell carcinoma (ESCC) and its correlation with clinicopathologic features and patient survival.

Methods: The expression profile of Ku80 was analyzed in 126 cases of locally advanced ESCC and 79 cases of normal subjects as control using immunohistochemistry and Western blot. The associations of Ku80 expression with clinicopathological features were estimated by χ (2) test. We further performed univariate and multivariate analyses to identify prognostic factors for overall survival (OS) of patients.

Results: Immunohistochemistry and Western blot analyses both showed the Ku80 protein expression was significantly higher in ESCC than normal esophageal mucosa and corresponding healthy esophageal mucosa. Statistical analysis suggested a significant correlation of Ku80 overexpression with the tumor size (p = 0.037), differentiation degree (p = 0.018), depth of invasion (p = 0.020), lymph node metastasis (p = 0.045), clinicopathological staging (p = 0.001), and tumor recurrence (p = 0.011) in locally advanced ESCC patients. Moreover, overexpression of Ku80 was associated with reduced OS of patients after surgery (p = 0.001). Multivariate analysis with a Cox proportional hazards model further suggested that Ku80 expression was an independent prognostic indicator for patients' OS (p = 0.029).

Conclusions: Ku80 was a predictor of tumor's progression and prognosis of locally advanced ESCC patients. All of these results indicate that assessment of Ku80 level could improve stratification of locally advanced ESCC patients.

MeSH terms

  • Antigens, Nuclear / genetics
  • Antigens, Nuclear / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Disease Progression
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology*
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Humans
  • Immunohistochemistry
  • Ku Autoantigen
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Proportional Hazards Models

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Xrcc6 protein, human
  • Ku Autoantigen