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

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.

• Authors: Bolag Altan, Takehiko Yokobori, Munenori Ide, Tuya Bai, Toru Yanoma, Akiharu Kimura, Norimichi Kogure, Masaki Suzuki, Pinjie Bao, Erito Mochiki, Kyoichi Ogata, Tadashi Handa, Kyoichi Kaira, Masahiko Nishiyama, Takayuki Asao, Tetsunari Oyama, Hiroyuki Kuwano
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 10 Pg. 5237-5247 (10 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 27798884 (Publication Type: Journal Article)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• 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

Topics

• 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, metabolism)
• Tegafur (therapeutic use)