Bolag Altan1,2, Takehiko Yokobori1,3, Munenori Ide4, Tuya Bai5, Toru Yanoma5, Akiharu Kimura5, Norimichi Kogure5, Masaki Suzuki5, Pinjie Bao5, Erito Mochiki6, Kyoichi Ogata5, Tadashi Handa4, Kyoichi Kaira2, Masahiko Nishiyama3, Takayuki Asao7, Tetsunari Oyama4, Hiroyuki Kuwano5. 1. Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan altanbolag@gunma-u.ac.jp bori45@gunma-u.ac.jp. 2. Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Gunma, Japan. 3. Department of Molecular Pharmacology and Oncology, Gunma University Graduate School of Medicine, Gunma, Japan. 4. Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Gunma, Japan. 5. Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan. 6. Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan. 7. Big Data Center for Intergrative Analysis, Gunma University Initiative for Advance Research, Maebashi, Gunma, Japan.
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. Copyright
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 humancancer. MATERIALS AND METHODS: We investigated the expression of MRN complex in humangastric 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. Copyright
Authors: Vincent Ho; Liping Chung; Amandeep Singh; Vivienne Lea; Askar Abubakar; Stephanie H Lim; Weng Ng; Mark Lee; Paul de Souza; Joo-Shik Shin; Cheok Soon Lee Journal: BMC Cancer Date: 2018-09-03 Impact factor: 4.430