The value of FATS expression in predicting sensitivity to radiotherapy in breast cancer

// Jun Zhang 1, * , Nan Wu 1, * , Tiemei Zhang 2 , Tao Sun 3 , Yi Su 3 , Jing Zhao 1 , Kun Mu 1 , Zhao Jin 1 , Ming Gao 4 , Juntian Liu 1 , Lin Gu 1 1 Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China 2 Department of Endoscopy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China 3 Department of Breast Surgery, Hebei Province Cangzhou City Nanpi People’s Hospital, Cangzhou 061500, China 4 Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China * These authors contributed equally to this work Correspondence to: Ming Gao, email: headandneck15@aliyun.com Lin Gu, email: doctorgulin@163.com Juntian Liu, email: Ljt641024@163.com Keywords: breast cancer, radiotherapy, FATS, biomarker Received: November 14, 2016      Accepted: March 01, 2017      Published: March 28, 2017 ABSTRACT Purpose: The fragile-site associated tumor suppressor (FATS) is a newly identified tumor suppressor involved in radiation-induced tumorigenesis. The purpose of this study was to characterize FATS expression in breast cancers about radiotherapy benefit, patient characteristics, and prognosis. Results: The expression of FATS mRNA was silent or downregulated in 95.2% of breast cancer samples compared with paired normal controls ( P < .0001). Negative status of FATS was correlated with higher nuclear grade ( P = .01) and shorter disease-free survival (DFS) of breast cancer ( P = .036). In a multivariate analysis, FATS expression showed favorable prognostic value for DFS (odds ratio, 0.532; 95% confidence interval, 0.299 to 0.947; ( P = .032). Furthermore, improved survival time was seen in FATS-positive patients receiving radiotherapy ( P = .006). The results of multivariate analysis revealed independent prognostic value of FATS expression in predicting longer DFS (odds ratio, 0.377; 95% confidence interval, 0.176 to 0.809; P = 0.012) for patients receiving adjuvant radiotherapy. In support of this, reduction of FATS expression in breast cancer cell lines, FATS positive group significantly sensitized than Knock-down of FATS group. Materials and Methods: Tissue samples from 156 breast cancer patients and 42 controls in tumor bank were studied. FATS gene expression was evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). FATS function was examined in breast cancer cell lines using siRNA knock-downs and colony forming assays after irradiation. Conclusions: FATS status is a biomarker in breast cancer to identify individuals likely to benefit from radiotherapy.