机构：[1]School of Medicine, Nankai University, Tianjin, China[2]Department of Breast &Thyroid Surgery, The Third People’s Hospital of Chengdu, The AffiliatedHospital of Southwest Jiaotong University, The Second Chengdu HospitalAffiliated to Chongqing Medical University, Chengdu, Sichuan, China[3]Sichuanhospital & Institute, Sichuan cancer center, School of Medicine, University ofElectronic Science and Technology of China, Chengdu, Sichuan, China四川省肿瘤医院[4]Department of Radiology, The Third People’s Hospital of Chengdu, TheAffiliated Hospital of Southwest Jiaotong University, The Second ChengduHospital Affiliated to Chongqing Medical University, Chengdu, Sichuan, China[5]The Key Laboratory of Weak-Light Nonlinear Photonics of Education Ministry,School of Physics and TEDA Institute of Applied Physics, Nankai University,Tianjin, China[6]2011Project Collaborative Innovation Center for Biotherapy ofMinistry of Education, Tianjin, China
The concept of breast-conserving surgery is a remarkable achievement of breast cancer therapy. Neoadjuvant chemotherapy is being used increasingly to shrink the tumor prior to surgery. Neoadjuvant chemotherapy is reducing the tumor size to make the surgery with less damaging to surrounding tissue and downstage locally inoperable disease to operable. However, non-effective neoadjuvant chemotherapy could increase the risks of delaying surgery, develop unresectable disease and metastatic tumor spread. The biomarkers for predicting the neoadjuvant chemotherapy effect are scarce in breast cancer treatment. In this study, we identified that FZR1 can be a novel biomarker for breast cancer neoadjuvant chemotherapy according to clinical patient cohort evaluation and molecular mechanism investigation. Transcriptomic data analysis indicated that the expression of FZR1 is correlated with the effect of neoadjuvant chemotherapy. Mechanistically, we demonstrate that FZR1 is pivotal to the chemotherapy drugs induced apoptosis and cell cycle arrest. FZR1 is involved in the stability of p53 by impairing the phosphorylation at ser15 site. We demonstrate that the expression of FZR1 detected by quantification of IHC can be an effective predictor of neoadjuvant chemotherapy in animal experiment and clinical patient cohort. To obtain more benefit for breast cancer patient, we propose that the FZR1 IHC score using at the clinical to predict the effect of neoadjuvant chemotherapy.
基金：
This work was supported by the National Natural Science Foundation of China(Grant No. 81773120, 81702963, 81972882), the Fundamental Research Funds for the Central Universities, Nankai University (No. 63191214), the State Commission of Science Technology of China Projects (2018YFE0114300).
第一作者机构：[1]School of Medicine, Nankai University, Tianjin, China
共同第一作者：
通讯作者：
通讯机构：[1]School of Medicine, Nankai University, Tianjin, China[6]2011Project Collaborative Innovation Center for Biotherapy ofMinistry of Education, Tianjin, China
推荐引用方式(GB/T 7714)：
Shuo Liu,Haobin Wang,Jun Li,et al.FZR1 as a novel biomarker for breast cancer neoadjuvant chemotherapy prediction.[J].CELL DEATH & DISEASE.2020,11(9):doi:10.1038/s41419-020-03004-9.
APA：
Shuo Liu,Haobin Wang,Jun Li,Jianhui Zhang,Jian Wu...&Shijing Yue.(2020).FZR1 as a novel biomarker for breast cancer neoadjuvant chemotherapy prediction..CELL DEATH & DISEASE,11,(9)
MLA：
Shuo Liu,et al."FZR1 as a novel biomarker for breast cancer neoadjuvant chemotherapy prediction.".CELL DEATH & DISEASE 11..9(2020)
生物学