Expression of Ku80 in cervical cancer correlates with response to radiotherapy and survival

Am J Clin Oncol. 2003 Aug;26(4):e80-5. doi: 10.1097/01.COC.0000077938.48974.59.

Abstract

To reveal the genes relevant for prediction of cervical cancer after radiotherapy, we previously carried out cDNA microarray experiments on primary cervical cancer comparing patients with a complete response (CR) and those with no change (NC). Some of these genes had already been associated with the radiation response, such as x-ray repair cross-complementing 5 (XRCC5), which was found more in radioresistant tumors than in radiosensitive ones. The aim of this study was to confirm the possible roles of XRCC5 mRNA levels by a real-time polymerase chain reaction method in 20 cervical cancers, and Ku80 protein, which is the gene product of XRCC5, using a histopathologic method of formalin-fixed sections of tumor biopsies in determining tumor response to radiotherapy and survival in 89 patients with cervical cancer. The levels of XRCC5 mRNA were 10(4.82) +/- 10(0.2) copies/microg total RNA in tumor tissues in the CR group (mean +/- standard deviation) and 10(4.95) +/- 10(0.32) copies/microg total RNA in those in the NC group. The levels of XRCC5 mRNA were not significantly different between the CR and NC groups. Histopathologic methods revealed 29.2% (26 of 89) of the patients to be Ku80-negative, with Ku80-positive findings in 70.8% (63 of 89). Of the Ku80-negative patients, 19 had CR, 3 had a partial response (PR), and 4 had NC. Of the Ku80-positive patients, 25 had CR, 22 had PR, and 16 had NC. Ku80-negative tumors showed significantly better responses than Ku80-positive ones, comparing CR and PR/NC responses (p = 0.01). In addition, overall survival was significantly better in the Ku80-negative patients as compared with those who were Ku80-positive (p = 0.04). The results of this study suggest that a low expression of Ku80 protein leads to radiosensitivity in cervical cancer and that Ku80 might play a role in treatment outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Nuclear / metabolism*
  • Brachytherapy
  • DNA Helicases*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Ku Autoantigen
  • Middle Aged
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Radiation Tolerance
  • Radiotherapy Dosage
  • Survival Analysis
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • RNA, Messenger
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Ku Autoantigen