High Expression of MRE11-RAD50-NBS1 Is Associated with Poor Prognosis and Chemoresistance in Gastric Cancer

Anticancer Res. 2016 Oct;36(10):5237-5247. doi: 10.21873/anticanres.11094.

Abstract

Background: The MRN complex of meiotic recombination 11 (MRE11), DNA repair protein Rad50 (RAD50) and Nijmegen breakage syndrome 1 (NBS1) proteins coordinate the detection and repair of DNA double-strand breaks (DSBs). DNA DSB repair-dependent chemoresistance likely has an effect on the treatment of human cancer.

Materials and methods: We investigated the expression of MRN complex in human gastric cancer (GC) tissues using immunohistochemistry and analyzed its clinical significance and prognostic relevance.

Results: The expression of MRN complex was significantly associated with clinical factors including poorer prognosis and negatively associated with the expression of DNA damage marker phosphorylated H2A histone family, member X (γH2AX) in the nucleus. In the biopsy specimens, low expression of MRE11 correlated with good response to chemotherapy and surgical resection after down-staging by chemotherapy. Furthermore, the expression levels of MRE11 and RAD50 were independent predictors of surgical resection after chemotherapy.

Conclusion: The high expression of MRN complex constituents could be a predictor for poor prognosis and chemoresistance in GC.

Keywords: DSB; Double-strand break repair; MRN complex; cisplatin; paclitaxel.

MeSH terms

  • Acid Anhydride Hydrolases
  • Antimetabolites, Antineoplastic / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cell Cycle Proteins / metabolism*
  • Cisplatin / therapeutic use
  • DNA Repair Enzymes / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Drug Combinations
  • Drug Resistance, Neoplasm
  • Humans
  • MRE11 Homologue Protein
  • Nuclear Proteins / metabolism*
  • Oxonic Acid / therapeutic use
  • Paclitaxel / therapeutic use
  • Prognosis
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / metabolism*
  • Tegafur / therapeutic use

Substances

  • Antimetabolites, Antineoplastic
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Drug Combinations
  • MRE11 protein, human
  • NBN protein, human
  • Nuclear Proteins
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • MRE11 Homologue Protein
  • Acid Anhydride Hydrolases
  • RAD50 protein, human
  • DNA Repair Enzymes
  • Paclitaxel
  • Cisplatin