期刊
ANTICANCER RESEARCH
卷 36, 期 10, 页码 5237-5247出版社
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.11094
关键词
Double-strand break repair; DSB; MRN complex; cisplatin; paclitaxel
类别
资金
- Yakult Honsha Co. Ltd.
- Japan Society for the Promotion of Science (JSPS) [22591450, 22591449, 23591857, 15K10085]
- ministry of Education, Culture, Sports, Science and Technology of Japan
- Gunma University Initiative for Advanced Research (GIAR)
- Grants-in-Aid for Scientific Research [22591449] Funding Source: KAKEN
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 (gamma H2AX) 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.
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