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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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Tumor Biology

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.

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Acknowledgments

This study was supported by Doctor Supporting Foundation of Tianjin Medical University Cancer Institute and Hospital (Nos. B1302 and B1305) and the National Nature Science Foundation of China (Nos. 81401948, 81472182, and 81472797).

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Authors and Affiliations

  1. 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

    Xiuli Chen, Dong Qian, Jingjing Cheng, Yong Guan, Xiaofeng Ding, Jing Zeng, Xi Chen, Puchun Er, Furong Zhang, Na Zhao, Xiaocen Chen, Lujun Zhao, Zhiyong Yuan, Qingsong Pang & Ping Wang

  2. 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

    Bin Zhang

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  1. Xiuli Chen
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Correspondence to Dong Qian, Qingsong Pang or Ping Wang.

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Xiuli Chen, Dong Qian, and Jingjing Cheng contributed equally to this work.

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Chen, X., Qian, D., Cheng, J. et al. High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer. Tumor Biol. 37, 13489–13498 (2016). https://doi.org/10.1007/s13277-016-5192-x

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