High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer
Rad51c is critical for homologous recombination repair and genomic stability and may play roles in tumorigenesis and cancer therapy. We investigated the expression level and clinical significance of Rad51c in non-small cell lung cancer (NSCLC) and determined the effect of Rad51c on NSCLC cell chemos...
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| Veröffentlicht in: | Tumor biology 2016-10, Vol.37 (10), p.13489-13498 |
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| creator | Chen, Xiuli Qian, Dong Cheng, Jingjing Guan, Yong Zhang, Bin Ding, Xiaofeng Zeng, Jing Chen, Xi Er, Puchun Zhang, Furong Zhao, Na Chen, Xiaocen Zhao, Lujun Yuan, Zhiyong Pang, Qingsong Wang, Ping |
| description | Rad51c is critical for homologous recombination repair and genomic stability and may play roles in tumorigenesis and cancer therapy. We investigated the expression level and clinical significance of Rad51c in non-small cell lung cancer (NSCLC) and determined the effect of Rad51c on NSCLC cell chemosensitivity and radiosensitivity. Rad51c expression was detected using immunohistochemistry and was higher in NSCLC patient samples than in adjacent normal tissues. Kaplan–Meier analysis revealed that high Rad51c expression was an independent predictor of short overall survival (OS) and disease-free survival (DFS) in NSCLC patients receiving chemotherapy and/or radiotherapy. Furthermore, Rad51c knockdown increased the killing effect of ionizing radiation (IR) and enhanced cisplatin-induced apoptotic cells in NSCLC cells by disrupting the repair of cisplatin- and IR-induced DNA damage. In addition, ectopic expression of Rad51c dramatically enhanced NSCLC cell resistance to cisplatin and radiotherapy. These findings suggest that increased expression of Rad51c may confer resistance to chemotherapy and/or radiotherapy of NSCLC, and also be an independent prognostic factor for patient outcome. Therefore, targeting Rad51c may represent an improved therapeutic strategy for NSCLC patients with locally advanced disease. |
| doi_str_mv | 10.1007/s13277-016-5192-x |
| format | Article |
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We investigated the expression level and clinical significance of Rad51c in non-small cell lung cancer (NSCLC) and determined the effect of Rad51c on NSCLC cell chemosensitivity and radiosensitivity. Rad51c expression was detected using immunohistochemistry and was higher in NSCLC patient samples than in adjacent normal tissues. Kaplan–Meier analysis revealed that high Rad51c expression was an independent predictor of short overall survival (OS) and disease-free survival (DFS) in NSCLC patients receiving chemotherapy and/or radiotherapy. Furthermore, Rad51c knockdown increased the killing effect of ionizing radiation (IR) and enhanced cisplatin-induced apoptotic cells in NSCLC cells by disrupting the repair of cisplatin- and IR-induced DNA damage. In addition, ectopic expression of Rad51c dramatically enhanced NSCLC cell resistance to cisplatin and radiotherapy. These findings suggest that increased expression of Rad51c may confer resistance to chemotherapy and/or radiotherapy of NSCLC, and also be an independent prognostic factor for patient outcome. Therefore, targeting Rad51c may represent an improved therapeutic strategy for NSCLC patients with locally advanced disease.</description><identifier>ISSN: 1010-4283</identifier><identifier>EISSN: 1423-0380</identifier><identifier>DOI: 10.1007/s13277-016-5192-x</identifier><identifier>PMID: 27465554</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Adenocarcinoma - therapy ; Antineoplastic Agents - pharmacology ; Apoptosis ; Biomedical and Life Sciences ; Biomedicine ; Blotting, Western ; Cancer Research ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - therapy ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - therapy ; Case-Control Studies ; Cell Proliferation ; Chemoradiotherapy ; Chemotherapy ; Cisplatin - pharmacology ; DNA-Binding Proteins - metabolism ; Drug Resistance, Neoplasm ; Female ; Flow Cytometry ; Fluorescent Antibody Technique ; Follow-Up Studies ; Gene expression ; Humans ; Immunoenzyme Techniques ; Lung cancer ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Male ; Medical prognosis ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Original Article ; Prognosis ; Radiation therapy ; Radiation Tolerance ; Survival Rate ; Tumor Cells, Cultured</subject><ispartof>Tumor biology, 2016-10, Vol.37 (10), p.13489-13498</ispartof><rights>International Society of Oncology and BioMarkers (ISOBM) 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-7082f769a9d8e98d578f252b8e21c33f983e2aa37b5978bd66d348b5c12fc3da3</citedby><cites>FETCH-LOGICAL-c438t-7082f769a9d8e98d578f252b8e21c33f983e2aa37b5978bd66d348b5c12fc3da3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13277-016-5192-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13277-016-5192-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27465554$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiuli</creatorcontrib><creatorcontrib>Qian, Dong</creatorcontrib><creatorcontrib>Cheng, Jingjing</creatorcontrib><creatorcontrib>Guan, Yong</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Ding, Xiaofeng</creatorcontrib><creatorcontrib>Zeng, Jing</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Er, Puchun</creatorcontrib><creatorcontrib>Zhang, Furong</creatorcontrib><creatorcontrib>Zhao, Na</creatorcontrib><creatorcontrib>Chen, Xiaocen</creatorcontrib><creatorcontrib>Zhao, Lujun</creatorcontrib><creatorcontrib>Yuan, Zhiyong</creatorcontrib><creatorcontrib>Pang, Qingsong</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><title>High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer</title><title>Tumor biology</title><addtitle>Tumor Biol</addtitle><addtitle>Tumour Biol</addtitle><description>Rad51c is critical for homologous recombination repair and genomic stability and may play roles in tumorigenesis and cancer therapy. We investigated the expression level and clinical significance of Rad51c in non-small cell lung cancer (NSCLC) and determined the effect of Rad51c on NSCLC cell chemosensitivity and radiosensitivity. Rad51c expression was detected using immunohistochemistry and was higher in NSCLC patient samples than in adjacent normal tissues. Kaplan–Meier analysis revealed that high Rad51c expression was an independent predictor of short overall survival (OS) and disease-free survival (DFS) in NSCLC patients receiving chemotherapy and/or radiotherapy. Furthermore, Rad51c knockdown increased the killing effect of ionizing radiation (IR) and enhanced cisplatin-induced apoptotic cells in NSCLC cells by disrupting the repair of cisplatin- and IR-induced DNA damage. In addition, ectopic expression of Rad51c dramatically enhanced NSCLC cell resistance to cisplatin and radiotherapy. These findings suggest that increased expression of Rad51c may confer resistance to chemotherapy and/or radiotherapy of NSCLC, and also be an independent prognostic factor for patient outcome. Therefore, targeting Rad51c may represent an improved therapeutic strategy for NSCLC patients with locally advanced disease.</description><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Adenocarcinoma - therapy</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blotting, Western</subject><subject>Cancer Research</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - therapy</subject><subject>Case-Control Studies</subject><subject>Cell Proliferation</subject><subject>Chemoradiotherapy</subject><subject>Chemotherapy</subject><subject>Cisplatin - pharmacology</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Drug Resistance, Neoplasm</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Fluorescent Antibody Technique</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Staging</subject><subject>Original Article</subject><subject>Prognosis</subject><subject>Radiation therapy</subject><subject>Radiation Tolerance</subject><subject>Survival Rate</subject><subject>Tumor Cells, Cultured</subject><issn>1010-4283</issn><issn>1423-0380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc2KFTEQhYMozjj6AG4k4MZNND-dTnopgzrCgCC6Dukkfc3QnVxT3XDnKXxl684dRQZcJVX5zqkKh5CXgr8VnJt3IJQ0hnHRMy0GyQ6PyLnopGJcWf4Y71xw1kmrzsgzgBvOhR6G_ik5k6brtdbdOfl1lXc_aDrsWwLItdA60a8-ahEotmIOK9B9rQ2ruisV1hxo3dZQl0R9iTSXuIUENKR5puiRYfUlJLpWGjLsZ7_mcgc2HzMWOAEbpRYGi0fJnW7eyo6Go649J08mP0N6cX9ekO8fP3y7vGLXXz59vnx_zUKn7MoMt3Iy_eCHaNNgozZ2klqONkkRlJoGq5L0XplRD8aOse-j6uyog5BTUNGrC_Lm5Iv_-rklWN2S4biML6lu4ISVvVESxyD6-gF6U7dWcDukVC80N0YhJU5UaBWgpcntW158u3WCu2Na7pSWw7TcMS13QM2re-dtXFL8q_gTDwLyBAA-lV1q_4z-r-tvR1ehuA</recordid><startdate>20161001</startdate><enddate>20161001</enddate><creator>Chen, Xiuli</creator><creator>Qian, Dong</creator><creator>Cheng, Jingjing</creator><creator>Guan, Yong</creator><creator>Zhang, Bin</creator><creator>Ding, Xiaofeng</creator><creator>Zeng, Jing</creator><creator>Chen, Xi</creator><creator>Er, Puchun</creator><creator>Zhang, Furong</creator><creator>Zhao, Na</creator><creator>Chen, Xiaocen</creator><creator>Zhao, Lujun</creator><creator>Yuan, Zhiyong</creator><creator>Pang, Qingsong</creator><creator>Wang, Ping</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>20161001</creationdate><title>High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer</title><author>Chen, Xiuli ; Qian, Dong ; Cheng, Jingjing ; Guan, Yong ; Zhang, Bin ; Ding, Xiaofeng ; Zeng, Jing ; Chen, Xi ; Er, Puchun ; Zhang, Furong ; Zhao, Na ; Chen, Xiaocen ; Zhao, Lujun ; Yuan, Zhiyong ; Pang, Qingsong ; Wang, Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-7082f769a9d8e98d578f252b8e21c33f983e2aa37b5978bd66d348b5c12fc3da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adenocarcinoma - metabolism</topic><topic>Adenocarcinoma - pathology</topic><topic>Adenocarcinoma - therapy</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Blotting, Western</topic><topic>Cancer Research</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - therapy</topic><topic>Case-Control Studies</topic><topic>Cell Proliferation</topic><topic>Chemoradiotherapy</topic><topic>Chemotherapy</topic><topic>Cisplatin - pharmacology</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Drug Resistance, Neoplasm</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Fluorescent Antibody Technique</topic><topic>Follow-Up Studies</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Middle Aged</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Staging</topic><topic>Original Article</topic><topic>Prognosis</topic><topic>Radiation therapy</topic><topic>Radiation Tolerance</topic><topic>Survival Rate</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiuli</creatorcontrib><creatorcontrib>Qian, Dong</creatorcontrib><creatorcontrib>Cheng, Jingjing</creatorcontrib><creatorcontrib>Guan, Yong</creatorcontrib><creatorcontrib>Zhang, Bin</creatorcontrib><creatorcontrib>Ding, Xiaofeng</creatorcontrib><creatorcontrib>Zeng, Jing</creatorcontrib><creatorcontrib>Chen, Xi</creatorcontrib><creatorcontrib>Er, Puchun</creatorcontrib><creatorcontrib>Zhang, Furong</creatorcontrib><creatorcontrib>Zhao, Na</creatorcontrib><creatorcontrib>Chen, Xiaocen</creatorcontrib><creatorcontrib>Zhao, Lujun</creatorcontrib><creatorcontrib>Yuan, Zhiyong</creatorcontrib><creatorcontrib>Pang, Qingsong</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Tumor biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiuli</au><au>Qian, Dong</au><au>Cheng, Jingjing</au><au>Guan, Yong</au><au>Zhang, Bin</au><au>Ding, Xiaofeng</au><au>Zeng, Jing</au><au>Chen, Xi</au><au>Er, Puchun</au><au>Zhang, Furong</au><au>Zhao, Na</au><au>Chen, Xiaocen</au><au>Zhao, Lujun</au><au>Yuan, Zhiyong</au><au>Pang, Qingsong</au><au>Wang, Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer</atitle><jtitle>Tumor biology</jtitle><stitle>Tumor Biol</stitle><addtitle>Tumour Biol</addtitle><date>2016-10-01</date><risdate>2016</risdate><volume>37</volume><issue>10</issue><spage>13489</spage><epage>13498</epage><pages>13489-13498</pages><issn>1010-4283</issn><eissn>1423-0380</eissn><abstract>Rad51c is critical for homologous recombination repair and genomic stability and may play roles in tumorigenesis and cancer therapy. We investigated the expression level and clinical significance of Rad51c in non-small cell lung cancer (NSCLC) and determined the effect of Rad51c on NSCLC cell chemosensitivity and radiosensitivity. Rad51c expression was detected using immunohistochemistry and was higher in NSCLC patient samples than in adjacent normal tissues. Kaplan–Meier analysis revealed that high Rad51c expression was an independent predictor of short overall survival (OS) and disease-free survival (DFS) in NSCLC patients receiving chemotherapy and/or radiotherapy. Furthermore, Rad51c knockdown increased the killing effect of ionizing radiation (IR) and enhanced cisplatin-induced apoptotic cells in NSCLC cells by disrupting the repair of cisplatin- and IR-induced DNA damage. In addition, ectopic expression of Rad51c dramatically enhanced NSCLC cell resistance to cisplatin and radiotherapy. These findings suggest that increased expression of Rad51c may confer resistance to chemotherapy and/or radiotherapy of NSCLC, and also be an independent prognostic factor for patient outcome. Therefore, targeting Rad51c may represent an improved therapeutic strategy for NSCLC patients with locally advanced disease.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>27465554</pmid><doi>10.1007/s13277-016-5192-x</doi><tpages>10</tpages></addata></record> |
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| subjects | Adenocarcinoma - metabolism Adenocarcinoma - pathology Adenocarcinoma - therapy Antineoplastic Agents - pharmacology Apoptosis Biomedical and Life Sciences Biomedicine Blotting, Western Cancer Research Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - therapy Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - therapy Case-Control Studies Cell Proliferation Chemoradiotherapy Chemotherapy Cisplatin - pharmacology DNA-Binding Proteins - metabolism Drug Resistance, Neoplasm Female Flow Cytometry Fluorescent Antibody Technique Follow-Up Studies Gene expression Humans Immunoenzyme Techniques Lung cancer Lung Neoplasms - metabolism Lung Neoplasms - pathology Lung Neoplasms - therapy Male Medical prognosis Middle Aged Neoplasm Grading Neoplasm Staging Original Article Prognosis Radiation therapy Radiation Tolerance Survival Rate Tumor Cells, Cultured |
| title | High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer |
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