A serum microRNA signature predicts trastuzumab benefit in HER2-positive metastatic breast cancer patients

Huiping Li, Jiang Liu, Jianing Chen, Huiyun Wang, Linbin Yang, Fei Chen, Siting Fan, Jing Wang, Bin Shao, Dong Yin, Musheng Zeng, Mengfeng Li, Jun Li, Fengxi Su, Qiang Liu, Herui Yao, Shicheng Su () and Erwei Song ()
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Huiping Li: Peking University Cancer Hospital and Institute
Jiang Liu: Sun Yat-sen University
Jianing Chen: Sun Yat-sen University
Huiyun Wang: Sun Yat-sen University
Linbin Yang: Sun Yat-sen University
Fei Chen: Sun Yat-sen University
Siting Fan: Sun Yat-sen University
Jing Wang: Peking University Cancer Hospital and Institute
Bin Shao: Peking University Cancer Hospital and Institute
Dong Yin: Sun Yat-sen University
Musheng Zeng: Sun Yat-sen University
Mengfeng Li: Sun Yat-sen University
Jun Li: Sun Yat-sen University
Fengxi Su: Sun Yat-sen University
Qiang Liu: Sun Yat-sen University
Herui Yao: Sun Yat-sen University
Shicheng Su: Sun Yat-sen University
Erwei Song: Sun Yat-sen University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Trastuzumab is a standard treatment for HER2-positive (HER2+) breast cancer, but some patients are refractory to the therapy. MicroRNAs (miRNAs) have been used to predict therapeutic effects for various cancers, but whether miRNAs can serve as biomarkers for HER2+ metastatic breast cancer (MBC) patients remains unclear. Using miRNA microarray, we identify 13 differentially expressed miRNAs in the serum of HER2+ MBC patients with distinct response to trastuzumab, and four miRNAs are selected to construct a signature to predict survival using LASSO model. Further, our data show that miR-940 is mainly released from the tumor cells and miR-451a, miR-16-5p and miR-17-3p are mainly from the immune cells. All these four miRNAs directly target signaling molecules that play crucial roles in regulating trastuzumab resistance. In summary, we develop a serum-based miRNA signature that potentially predicts the therapeutic benefit of trastuzumab for HER2+ MBC patients and warrants future validation in prospective clinical trials.

Date: 2018
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DOI: 10.1038/s41467-018-03537-w

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