Oncotarget

Research Papers:

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

Jun Zhang, Nan Wu, Tiemei Zhang, Tao Sun, Yi Su, Jing Zhao, Kun Mu, Zhao Jin, Ming Gao, Juntian Liu and Lin Gu _

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Oncotarget. 2017; 8:38491-38500. https://doi.org/10.18632/oncotarget.16630

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Abstract

Jun Zhang1,*, Nan Wu1,*, Tiemei Zhang2, Tao Sun3, Yi Su3, Jing Zhao1, Kun Mu1, Zhao Jin1, Ming Gao4, Juntian Liu1, Lin Gu1

1Department 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

2Department 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

3Department of Breast Surgery, Hebei Province Cangzhou City Nanpi People’s Hospital, Cangzhou 061500, China

4Department 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.


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