High expression of Rad51c predicts poor prognostic outcome and induces cell resistance to cisplatin and radiation in non-small cell lung cancer
- PMID: 27465554
- DOI: 10.1007/s13277-016-5192-x
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.
Keywords: Chemotherapy; DNA damage repair; Non-small cell lung cancer; Prognosis; Rad51c; Radiotherapy.
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