Expression of DNA double-strand break repair proteins predicts the response and prognosis of colorectal cancer patients undergoing oxaliplatin-based chemotherapy
DNA intrastrand cross-linking agents such as oxaliplatin induce DNA double-strand breaks (DSBs) during DNA repair and replication. In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Sev...
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| Veröffentlicht in: | Oncology reports 2016-03, Vol.35 (3), p.1349-1355 |
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| creator | IHARA, KEISUKE YAMAGUCHI, SATORU UENO, NOZOMI TANI, YUKIKO SHIDA, YOSUKE OGATA, HIDEO DOMEKI, YASUSHI OKAMOTO, KENTARO NAKAJIMA, MASANOBU SASAKI, KINRO TSUCHIOKA, TAKASHI MITOMI, HIROYUKI KATO, HIROYUKI |
| description | DNA intrastrand cross-linking agents such as oxaliplatin induce DNA double-strand breaks (DSBs) during DNA repair and replication. In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Seventy-eight patients with metastatic or recurrent colorectal cancer who had measurable target lesions and who underwent resection for primary colorectal cancer in our institution between April 2007 and March 2013 were included in the present study. The median age was 64.5 years, and the cohort consisted of 49 males and 29 females. The median progression-free survival (PFS) was 10.9 months. The expression of DSB repair proteins such as RAD51 and MRE11 was investigated by immunohistochemistry, and associations between RAD51 and MRE11 expression and clinicopathological factors or chemotherapeutic effect were assessed. MRE11-negative cases and RAD51-negative cases achieved significantly better tumor reduction compared with cases with positive expression. Cases with negative expression of both proteins or negative expression of either protein had significantly longer PFS than cases with positive expression for both proteins. In conclusion, DSB repair protein expression-negative colorectal cancer cases may be more highly sensitive to chemotherapy, and thus DSB repair protein expression may be a useful prognostic indicator for colorectal cancer patients. |
| doi_str_mv | 10.3892/or.2015.4488 |
| format | Article |
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In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Seventy-eight patients with metastatic or recurrent colorectal cancer who had measurable target lesions and who underwent resection for primary colorectal cancer in our institution between April 2007 and March 2013 were included in the present study. The median age was 64.5 years, and the cohort consisted of 49 males and 29 females. The median progression-free survival (PFS) was 10.9 months. The expression of DSB repair proteins such as RAD51 and MRE11 was investigated by immunohistochemistry, and associations between RAD51 and MRE11 expression and clinicopathological factors or chemotherapeutic effect were assessed. MRE11-negative cases and RAD51-negative cases achieved significantly better tumor reduction compared with cases with positive expression. Cases with negative expression of both proteins or negative expression of either protein had significantly longer PFS than cases with positive expression for both proteins. In conclusion, DSB repair protein expression-negative colorectal cancer cases may be more highly sensitive to chemotherapy, and thus DSB repair protein expression may be a useful prognostic indicator for colorectal cancer patients.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2015.4488</identifier><identifier>PMID: 26676960</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Adult ; Age ; Aged ; Biomarkers ; Cancer therapies ; Chemotherapy ; Colorectal cancer ; Colorectal Neoplasms - drug therapy ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Deoxyribonucleic acid ; Development and progression ; Disease-Free Survival ; DNA ; DNA Breaks, Double-Stranded - drug effects ; DNA damage ; DNA Damage - genetics ; DNA Repair - genetics ; DNA-Binding Proteins - biosynthesis ; DNA-Binding Proteins - genetics ; Drug metabolism ; DSB repair protein expression pattern ; Female ; Females ; Gender ; Gene expression ; Gene Expression Regulation, Neoplastic - drug effects ; Genetic aspects ; Growth factors ; Health aspects ; Histology ; Humans ; immunohistochemistry ; Male ; Medical prognosis ; Metastasis ; Middle Aged ; MRE11 ; MRE11 Homologue Protein ; Multivariate analysis ; Neoplasm Recurrence, Local - drug therapy ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - pathology ; Organoplatinum Compounds - administration & dosage ; Oxaliplatin ; Patients ; Prognosis ; Protein expression ; Proteins ; RAD51 ; Rad51 Recombinase - biosynthesis ; Rad51 Recombinase - genetics ; Rodents</subject><ispartof>Oncology reports, 2016-03, Vol.35 (3), p.1349-1355</ispartof><rights>Copyright © 2016, Spandidos Publications</rights><rights>COPYRIGHT 2016 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c552t-2eb078190dc5087893d1063bb05ec0ad4b2af4163bf2f592fdb490c7937152b63</citedby><cites>FETCH-LOGICAL-c552t-2eb078190dc5087893d1063bb05ec0ad4b2af4163bf2f592fdb490c7937152b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26676960$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>IHARA, KEISUKE</creatorcontrib><creatorcontrib>YAMAGUCHI, SATORU</creatorcontrib><creatorcontrib>UENO, NOZOMI</creatorcontrib><creatorcontrib>TANI, YUKIKO</creatorcontrib><creatorcontrib>SHIDA, YOSUKE</creatorcontrib><creatorcontrib>OGATA, HIDEO</creatorcontrib><creatorcontrib>DOMEKI, YASUSHI</creatorcontrib><creatorcontrib>OKAMOTO, KENTARO</creatorcontrib><creatorcontrib>NAKAJIMA, MASANOBU</creatorcontrib><creatorcontrib>SASAKI, KINRO</creatorcontrib><creatorcontrib>TSUCHIOKA, TAKASHI</creatorcontrib><creatorcontrib>MITOMI, HIROYUKI</creatorcontrib><creatorcontrib>KATO, HIROYUKI</creatorcontrib><title>Expression of DNA double-strand break repair proteins predicts the response and prognosis of colorectal cancer patients undergoing oxaliplatin-based chemotherapy</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>DNA intrastrand cross-linking agents such as oxaliplatin induce DNA double-strand breaks (DSBs) during DNA repair and replication. In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Seventy-eight patients with metastatic or recurrent colorectal cancer who had measurable target lesions and who underwent resection for primary colorectal cancer in our institution between April 2007 and March 2013 were included in the present study. The median age was 64.5 years, and the cohort consisted of 49 males and 29 females. The median progression-free survival (PFS) was 10.9 months. The expression of DSB repair proteins such as RAD51 and MRE11 was investigated by immunohistochemistry, and associations between RAD51 and MRE11 expression and clinicopathological factors or chemotherapeutic effect were assessed. MRE11-negative cases and RAD51-negative cases achieved significantly better tumor reduction compared with cases with positive expression. Cases with negative expression of both proteins or negative expression of either protein had significantly longer PFS than cases with positive expression for both proteins. In conclusion, DSB repair protein expression-negative colorectal cancer cases may be more highly sensitive to chemotherapy, and thus DSB repair protein expression may be a useful prognostic indicator for colorectal cancer patients.</description><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Biomarkers</subject><subject>Cancer therapies</subject><subject>Chemotherapy</subject><subject>Colorectal cancer</subject><subject>Colorectal Neoplasms - drug therapy</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>Disease-Free Survival</subject><subject>DNA</subject><subject>DNA Breaks, Double-Stranded - drug effects</subject><subject>DNA damage</subject><subject>DNA Damage - genetics</subject><subject>DNA Repair - genetics</subject><subject>DNA-Binding Proteins - biosynthesis</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Drug metabolism</subject><subject>DSB repair protein expression pattern</subject><subject>Female</subject><subject>Females</subject><subject>Gender</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Genetic aspects</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Histology</subject><subject>Humans</subject><subject>immunohistochemistry</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>MRE11</subject><subject>MRE11 Homologue Protein</subject><subject>Multivariate analysis</subject><subject>Neoplasm Recurrence, Local - drug therapy</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - pathology</subject><subject>Organoplatinum Compounds - administration & dosage</subject><subject>Oxaliplatin</subject><subject>Patients</subject><subject>Prognosis</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>RAD51</subject><subject>Rad51 Recombinase - biosynthesis</subject><subject>Rad51 Recombinase - genetics</subject><subject>Rodents</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptkk1v1DAQhiMEoqVw44wsISEOZPFXnPi4KuVDquACEjfLsSe7Llk7eBKp_Tn8Uxy1tBQhHzyaeeYdj2eq6jmjG9Fp_jblDaes2UjZdQ-qY9ZqVnMp2MNiU85qIZrvR9UTxAtKeUuVflwdcaVapRU9rn6dXU4ZEEOKJA3k3ect8WnpR6hxzjZ60mewP0iGyYZMppxmCBGLAT64Gcm8hxLEKUUEsvIF2cWEAVc5l8aUwc12JM5GB0XBzgFiSVyih7xLIe5IurRjmMYSiXVvETxxezikIp3tdPW0ejTYEeHZzX1SfXt_9vX0Y33-5cOn0-157ZqGzzWHnrYd09S7hnZtp4VnVIm-pw04ar3suR0kK56BD43mg--lpq7VomUN75U4qV5f65YOfi6AszkEdDCONkJa0LBWSaU7pWlBX_6DXqQlx_I6w7TgSgsqxR21syOYEIdUftStomYrZSspk1IXavMfqhwPh-BShCEU_72EV38l7MGO8x7TuMxlhHgffHMNupwQMwxmyuFg85Vh1KyrY1I26-qYdXUK_uKmqaU_gL-F_-zKXWGcyqCDT3jLpFyLpqaiZqIU_g2cu8xC</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>IHARA, KEISUKE</creator><creator>YAMAGUCHI, SATORU</creator><creator>UENO, NOZOMI</creator><creator>TANI, YUKIKO</creator><creator>SHIDA, YOSUKE</creator><creator>OGATA, HIDEO</creator><creator>DOMEKI, YASUSHI</creator><creator>OKAMOTO, KENTARO</creator><creator>NAKAJIMA, MASANOBU</creator><creator>SASAKI, KINRO</creator><creator>TSUCHIOKA, TAKASHI</creator><creator>MITOMI, HIROYUKI</creator><creator>KATO, HIROYUKI</creator><general>D.A. 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drug therapy</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>Disease-Free Survival</topic><topic>DNA</topic><topic>DNA Breaks, Double-Stranded - drug effects</topic><topic>DNA damage</topic><topic>DNA Damage - genetics</topic><topic>DNA Repair - genetics</topic><topic>DNA-Binding Proteins - biosynthesis</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Drug metabolism</topic><topic>DSB repair protein expression pattern</topic><topic>Female</topic><topic>Females</topic><topic>Gender</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Genetic aspects</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Histology</topic><topic>Humans</topic><topic>immunohistochemistry</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>MRE11</topic><topic>MRE11 Homologue Protein</topic><topic>Multivariate analysis</topic><topic>Neoplasm Recurrence, Local - drug therapy</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - pathology</topic><topic>Organoplatinum Compounds - administration & dosage</topic><topic>Oxaliplatin</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>RAD51</topic><topic>Rad51 Recombinase - biosynthesis</topic><topic>Rad51 Recombinase - genetics</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>IHARA, KEISUKE</creatorcontrib><creatorcontrib>YAMAGUCHI, SATORU</creatorcontrib><creatorcontrib>UENO, NOZOMI</creatorcontrib><creatorcontrib>TANI, YUKIKO</creatorcontrib><creatorcontrib>SHIDA, YOSUKE</creatorcontrib><creatorcontrib>OGATA, HIDEO</creatorcontrib><creatorcontrib>DOMEKI, YASUSHI</creatorcontrib><creatorcontrib>OKAMOTO, KENTARO</creatorcontrib><creatorcontrib>NAKAJIMA, MASANOBU</creatorcontrib><creatorcontrib>SASAKI, KINRO</creatorcontrib><creatorcontrib>TSUCHIOKA, TAKASHI</creatorcontrib><creatorcontrib>MITOMI, HIROYUKI</creatorcontrib><creatorcontrib>KATO, HIROYUKI</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>IHARA, KEISUKE</au><au>YAMAGUCHI, SATORU</au><au>UENO, NOZOMI</au><au>TANI, YUKIKO</au><au>SHIDA, YOSUKE</au><au>OGATA, HIDEO</au><au>DOMEKI, YASUSHI</au><au>OKAMOTO, KENTARO</au><au>NAKAJIMA, MASANOBU</au><au>SASAKI, KINRO</au><au>TSUCHIOKA, TAKASHI</au><au>MITOMI, HIROYUKI</au><au>KATO, HIROYUKI</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of DNA double-strand break repair proteins predicts the response and prognosis of colorectal cancer patients undergoing oxaliplatin-based chemotherapy</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>35</volume><issue>3</issue><spage>1349</spage><epage>1355</epage><pages>1349-1355</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>DNA intrastrand cross-linking agents such as oxaliplatin induce DNA double-strand breaks (DSBs) during DNA repair and replication. In the present study, we hypothesized that DNA intrastrand cross-linking agents may significantly benefit colorectal cancer patients with deficiencies in DSB repair. Seventy-eight patients with metastatic or recurrent colorectal cancer who had measurable target lesions and who underwent resection for primary colorectal cancer in our institution between April 2007 and March 2013 were included in the present study. The median age was 64.5 years, and the cohort consisted of 49 males and 29 females. The median progression-free survival (PFS) was 10.9 months. The expression of DSB repair proteins such as RAD51 and MRE11 was investigated by immunohistochemistry, and associations between RAD51 and MRE11 expression and clinicopathological factors or chemotherapeutic effect were assessed. MRE11-negative cases and RAD51-negative cases achieved significantly better tumor reduction compared with cases with positive expression. Cases with negative expression of both proteins or negative expression of either protein had significantly longer PFS than cases with positive expression for both proteins. In conclusion, DSB repair protein expression-negative colorectal cancer cases may be more highly sensitive to chemotherapy, and thus DSB repair protein expression may be a useful prognostic indicator for colorectal cancer patients.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26676960</pmid><doi>10.3892/or.2015.4488</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology reports, 2016-03, Vol.35 (3), p.1349-1355 |
| issn | 1021-335X 1791-2431 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Age Aged Biomarkers Cancer therapies Chemotherapy Colorectal cancer Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Deoxyribonucleic acid Development and progression Disease-Free Survival DNA DNA Breaks, Double-Stranded - drug effects DNA damage DNA Damage - genetics DNA Repair - genetics DNA-Binding Proteins - biosynthesis DNA-Binding Proteins - genetics Drug metabolism DSB repair protein expression pattern Female Females Gender Gene expression Gene Expression Regulation, Neoplastic - drug effects Genetic aspects Growth factors Health aspects Histology Humans immunohistochemistry Male Medical prognosis Metastasis Middle Aged MRE11 MRE11 Homologue Protein Multivariate analysis Neoplasm Recurrence, Local - drug therapy Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - pathology Organoplatinum Compounds - administration & dosage Oxaliplatin Patients Prognosis Protein expression Proteins RAD51 Rad51 Recombinase - biosynthesis Rad51 Recombinase - genetics Rodents |
| title | Expression of DNA double-strand break repair proteins predicts the response and prognosis of colorectal cancer patients undergoing oxaliplatin-based chemotherapy |
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