title: High Expression of MRE11-RAD50-NBS1 Is Associated with Poor Prognosis and Chemoresistance in Gastric Cancer.
abstract: 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.
  
  
  
  We investigated the expression of MRN complex in human gastric cancer (GC) tissues using immunohistochemistry and analyzed its clinical significance and prognostic relevance.
  
  
  
  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.
  
  
  
  The high expression of MRN complex constituents could be a predictor for poor prognosis and chemoresistance in GC.
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan altanbolag@gunma-u.ac.jp bori45@gunma-u.ac.jp.|Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Bolag
authors: B
authors: Altan
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan altanbolag@gunma-u.ac.jp bori45@gunma-u.ac.jp.|Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Takehiko
authors: T
authors: Yokobori
authors: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Munenori
authors: M
authors: Ide
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Tuya
authors: T
authors: Bai
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Toru
authors: T
authors: Yanoma
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Akiharu
authors: A
authors: Kimura
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Norimichi
authors: N
authors: Kogure
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Masaki
authors: M
authors: Suzuki
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Pinjie
authors: P
authors: Bao
authors: Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors: Erito
authors: E
authors: Mochiki
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Kyoichi
authors: K
authors: Ogata
authors: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Tadashi
authors: T
authors: Handa
authors: Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Kyoichi
authors: K
authors: Kaira
authors: Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Masahiko
authors: M
authors: Nishiyama
authors: Big Data Center for Intergrative Analysis, Gunma University Initiative for Advance Research, Maebashi, Gunma, Japan.
authors: Takayuki
authors: T
authors: Asao
authors: Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Tetsunari
authors: T
authors: Oyama
authors: Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan.
authors: Hiroyuki
authors: H
authors: Kuwano
mesh_terms: D017766:Acid Anhydride Hydrolases; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000627:therapeutic use; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000378:metabolism*; D010094:Oxonic Acid / Q000627:therapeutic use; D017239:Paclitaxel / Q000627:therapeutic use; D011379:Prognosis; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D005641:Tegafur / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004338:Drug Combinations; C121766:MRE11 protein, human; C112156:NBN protein, human; D009687:Nuclear Proteins; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000076228:MRE11 Homologue Protein; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes; D017239:Paclitaxel; D002945:Cisplatin
keywords: DSB; Double-strand break repair; MRN complex; cisplatin; paclitaxel