title: High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer.
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.
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China. qiankeyu1984@126.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Lung Cancer, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Puchun
authors.initials: P
authors.lastname: Er
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Xiaocen
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Lujun
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China. qingsongpang11@126.com.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Pang
authors.affiliation: Department of Radiotherapy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Street, Tianjin, 300060, China. wangping@tjmuch.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D049109:Cell Proliferation; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011836:Radiation Tolerance; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C448305:RAD51C protein, human; D002945:Cisplatin
keywords: Chemotherapy; DNA damage repair; Non-small cell lung cancer; Prognosis; Rad51c; Radiotherapy