TY - JOUR
T1 - ABTB2 Regulatory Variant as Predictor of Epirubicin-Based Neoadjuvant Chemotherapy in Luminal A Breast Cancer
AU - Gong, Yajie
AU - Hu, Nanlin
AU - Ma, Li
AU - Li, Wentong
AU - Cheng, Xiang
AU - Zhang, Yi
AU - Zhu, Ying
AU - Yang, Yang
AU - Peng, Xiating
AU - Zou, Danyi
AU - Tian, Jianbo
AU - Yang, Lan
AU - Mei, Shufang
AU - Wang, Xiaoyang
AU - Lo, Chun Han
AU - Chang, Jiang
AU - Hou, Tieying
AU - Zhang, Hong
AU - Xu, Binghe
AU - Zhong, Rong
AU - Yuan, Peng
N1 - Publisher Copyright:
© Copyright © 2020 Gong, Hu, Ma, Li, Cheng, Zhang, Zhu, Yang, Peng, Zou, Tian, Yang, Mei, Wang, Lo, Chang, Hou, Zhang, Xu, Zhong and Yuan.
PY - 2020/9/25
Y1 - 2020/9/25
N2 - 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/m2 and docetaxel 75 mg/m2 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 of ABTB2. Subsequent biological assays illustrated that upregulation of ABTB2 significantly reduced the apoptosis rate of breast cancer cells and enhanced the chemo-resistance to epirubicin. Conclusions: Our study demonstrated rs6484711 polymorphism regulating ABTB2 expression 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.
AB - 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/m2 and docetaxel 75 mg/m2 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 of ABTB2. Subsequent biological assays illustrated that upregulation of ABTB2 significantly reduced the apoptosis rate of breast cancer cells and enhanced the chemo-resistance to epirubicin. Conclusions: Our study demonstrated rs6484711 polymorphism regulating ABTB2 expression 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.
KW - ABTB2
KW - epirubicin resistance
KW - luminal A breast cancer
KW - neoadjuvant chemotherapy
KW - single nucleotide polymorphism
UR - https://www.scopus.com/pages/publications/85092307707
U2 - 10.3389/fonc.2020.571517
DO - 10.3389/fonc.2020.571517
M3 - 文章
AN - SCOPUS:85092307707
SN - 2234-943X
VL - 10
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 571517
ER -
