Development of triple-negative breast cancer radiosensitive gene signature and validation based on transcriptome analysis
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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.
KeywordsTriple-negative breast cancer Transcriptome analysis Radiosensitive gene signature
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 6.Group EBCTC (2006) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366(9503):2087–2106Google Scholar
- 7.Chen X, Yu X, Chen J, Yang Z, Shao Z, Zhang Z, Guo X, Feng Y (2013) Radiotherapy can improve the disease-free survival rate in triple-negative breast cancer patients with T1-T2 disease and one to three positive lymph nodes after mastectomy. Oncologist 18(2):141–147. doi: 10.1634/theoncologist.2012-0233 PubMedCentralCrossRefPubMedGoogle Scholar
- 8.Abdulkarim BS, Cuartero J, Hanson J, Deschênes J, Lesniak D, Sabri S (2011) Increased risk of locoregional recurrence for women with T1-2N0 triple-negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol 29(21):2852–2858CrossRefPubMedGoogle Scholar
- 10.Eschrich SA, Pramana J, Zhang H, Zhao H, Boulware D, Lee JH, Bloom G, Rocha-Lima C, Kelley S, Calvin DP, Yeatman TJ, Begg AC, Torres-Roca JF (2009) A gene expression model of intrinsic tumor radiosensitivity: prediction of response and prognosis after chemoradiation. Int J Radiat Oncol Biol Phys 75(2):489–496. doi: 10.1016/j.ijrobp.2009.06.014 PubMedCentralCrossRefPubMedGoogle Scholar
- 16.Kuo WH, Chang YY, Lai LC, Tsai MH, Hsiao CK, Chang KJ, Chuang EY (2012) Molecular characteristics and metastasis predictor genes of triple-negative breast cancer: a clinical study of triple-negative breast carcinomas. PLoS ONE 7(9):e45831. doi: 10.1371/journal.pone.0045831 PubMedCentralCrossRefPubMedGoogle Scholar
- 17.Eschrich SA, Fulp WJ, Pawitan Y, Foekens JA, Smid M, Martens JW, Echevarria M, Kamath V, Lee JH, Harris EE, Bergh J, Torres-Roca JF (2012) Validation of a radiosensitivity molecular signature in breast cancer. Clin Cancer Res 18(18):5134–5143. doi: 10.1158/1078-0432.CCR-12-0891 PubMedCentralCrossRefPubMedGoogle Scholar