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Development of triple-negative breast cancer radiosensitive gene signature and validation based on transcriptome analysis

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Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease with highest loco-regional recurrence among breast cancer subtypes. Radiotherapy is indispensable for TNBC loco-regional control. However, intrinsic radiosensitivity differences exist in TNBC patients and RT is still prescribed mainly based on conventional clinicopathologic features of patients without considering the differences. The purpose of the present study is to develop and validate a TNBC radiosensitive gene signature (RSGS) and to guide therapeutic decisions. In this study, we compared transcriptome profiles of 12 locally recurrent TNBCs to 20 non-locally recurrent TNBCs treated with surgery radio-chemotherapy and developed a seven-gene RSGS and a simplified three-gene RSGS by using pathway analysis, univariate Cox proportional hazards regression model and rank-based linear algorithm. They were validated by using transcriptome profiles of 166 TNBC patients. Two gene signatures specifically identified a radiosensitive population that had an improved recurrence-free survival in patients treated with surgery radio-chemotherapy (Radiosensitive patients vs radioresistant patients, for seven-gene RSGS: P = 0.024, HR = 0.35, 95 %CI 0.14–0.87 and for three-gene RSGS: P = 0.035, HR = 0.38, 95 %CI 0.15–0.94). In contrast, there was no significant difference in outcome between predicted radiosensitive and radioresistant patients that treated with other treatment modality. RSGSs provide a useful tool for identification of radiosensitive/radioresistant TNBC patients and they could lead to a better selection of patients for RT protocols.

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Acknowledgments

This study was supported by Project Funded by China Postdoctoral Science Foundation (2015M571493) and grants from the National Natural Science Foundation of China (81372848, 81370075). We are grateful to Dr. Kamila Abulimiti (MD) from Strayer University (USA) for checking the English of the manuscript.

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Authors and Affiliations

  1. Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, 270 Dong-An Road, Shanghai, 200032, China

    Alimujiang Wushou, Yi-Zhou Jiang, Yi-Rong Liu & Zhi-Ming Shao

  2. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China

    Jing Hou & Xiao-Mao Guo

  3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

    Alimujiang Wushou, Yi-Zhou Jiang, Jing Hou, Yi-Rong Liu, Xiao-Mao Guo & Zhi-Ming Shao

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  1. Alimujiang Wushou
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  2. Yi-Zhou Jiang
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  3. Jing Hou
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  4. Yi-Rong Liu
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  5. Xiao-Mao Guo
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  6. Zhi-Ming Shao
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Correspondence to Alimujiang Wushou or Zhi-Ming Shao.

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Wushou, A., Jiang, YZ., Hou, J. et al. Development of triple-negative breast cancer radiosensitive gene signature and validation based on transcriptome analysis. Breast Cancer Res Treat 154, 57–62 (2015). https://doi.org/10.1007/s10549-015-3611-0

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  • DOI: https://doi.org/10.1007/s10549-015-3611-0

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