机构：[1]Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School ofPublic Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,[2]Department ofClinical Laboratory Medicine, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences,Guangzhou, China,[3]Department of Medical Oncology, National Cancer Center, National Clinical Research Center for Cancer,Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China,[4]Department ofBreast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China,河北医科大学第四医院[5]Department of Hepatobiliary Surgery,Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,华中科技大学同济医学院附属协和医院[6]Department ofEpidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States,[7]Department of Pathology, MemorialSloan Kettering Cancer Center, New York, NY, United States,[8]Department of VIP Medical Services, National Cancer Center,National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking UnionMedical College, Beijing, China
Background:Epirubicin combined with docetaxel is the cornerstone of neoadjuvant chemotherapy (NAC) for breast cancer. The efficacy of NAC for luminal A breast cancer patients is very limited, and single nucleotide polymorphism is one of the most important factors that influences the efficacy. Our study is aimed to explore genetic markers for the efficacy of epirubicin combined with docetaxel for NAC in patients with luminal A breast cancer. Methods:A total of 421 patients with two stages of luminal A breast cancer were enrolled in this study from 2 centers. Among them 231 patients were included in the discovery cohort and 190 patients are in the replication cohort. All patients received epirubicin 75 mg/m(2)and docetaxel 75 mg/m(2)on day 1, in a 21-day cycle, a cycle for 2-6 cycles. Before treatment, 2 ml of peripheral blood was collected from each patient to isolate genomic DNA. Fourteen functional variants potentially regulating epirubicin/docetaxel response genes were prioritized by CellMiner and bioinformatics approaches. Moreover, biological assays were performed to determine the effect of genetic variations on response to chemotherapy. Results:The patients carrying rs6484711 variant A allele suffered a poor response to epirubicin and docetaxel for NAC (OR = 0.37, 95% CI: 0.18-0.74,P= 0.005) in combined stage. Moreover, expression quantitative trait loci (eQTL) analyses and luciferase reporter assays revealed that rs6484711 A allele significantly increased the expression ofABTB2. Subsequent biological assays illustrated that upregulation ofABTB2significantly reduced the apoptosis rate of breast cancer cells and enhanced the chemo-resistance to epirubicin. Conclusions:Our study demonstrated rs6484711 polymorphism regulatingABTB2expression might predict efficacy to epirubicin based NAC in luminal A breast cancer patients. These results provided valuable information about potential role of genetic variations in individualized chemotherapy.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC-81472753, NSFC-81402746]; National Key Research and Development Program of China [2016YFC1302702, 2016YFC1302703]
第一作者机构：[1]Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School ofPublic Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,[2]Department ofClinical Laboratory Medicine, Guangdong Provincial People’s Hospital and Guangdong Academy of Medical Sciences,Guangzhou, China,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School ofPublic Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China,[8]Department of VIP Medical Services, National Cancer Center,National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking UnionMedical College, Beijing, China
推荐引用方式(GB/T 7714)：
Yajie Gong,Nanlin Hu,Li Ma,et al.ABTB2Regulatory Variant as Predictor of Epirubicin-Based Neoadjuvant Chemotherapy in Luminal A Breast Cancer[J].FRONTIERS IN ONCOLOGY.2020,10:doi:10.3389/fonc.2020.571517.
APA：
Yajie Gong,Nanlin Hu,Li Ma,Wentong Li,Xiang Cheng...&Peng Yuan.(2020).ABTB2Regulatory Variant as Predictor of Epirubicin-Based Neoadjuvant Chemotherapy in Luminal A Breast Cancer.FRONTIERS IN ONCOLOGY,10,
MLA：
Yajie Gong,et al."ABTB2Regulatory Variant as Predictor of Epirubicin-Based Neoadjuvant Chemotherapy in Luminal A Breast Cancer".FRONTIERS IN ONCOLOGY 10.(2020)
