MNX1 Promotes Anti-HER2 Therapy Sensitivity via Transcriptional Regulation of CD-M6PR in HER2-Positive Breast Cancer

Author:

Chi Weiru12,Xiu Bingqiu12ORCID,Xiong Min12,Wang Xuliren12ORCID,Li Pei12,Zhang Qi12,Hou Jianjing12,Sang Yuting12,Zhou Xujie12,Chen Ming12,Zheng Shuyue12,Zhang Liyi12,Xue Jingyan12,Chi Yayun12,Wu Jiong12ORCID

Affiliation:

1. Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China

2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract

Although targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer has significantly prolonged survival time and improved patients’ quality of life, drug resistance has gradually emerged. This study explored the mechanisms underlying the effect of the motor neuron and pancreatic homeobox 1 (MNX1) genes on drug sensitivity in HER2-positive breast cancer. From July 2017 to 2018, core needle biopsies of HER2-positive breast cancer were collected from patients who received paclitaxel, carboplatin, and trastuzumab neoadjuvant therapy at our center. Based on treatment efficacy, 81 patients were divided into pathological complete response (pCR) and non-pCR groups. High-throughput RNA sequencing results were analyzed along with the GSE181574 dataset. MNX1 was significantly upregulated in the pCR group compared with the non-pCR group in both sequencing datasets, suggesting that MNX1 might be correlated with drug sensitivity in HER2-positive breast cancer. Meanwhile, tissue array results revealed that high MNX1 expression corresponded to a good prognosis. In vitro functional tests showed that upregulation of MNX1 significantly increased the sensitivity of HER2-positive breast cancer cells to lapatinib and pyrotinib. In conclusion, MNX1 may serve as a prognostic marker for patients with HER2-positive breast cancer, and its expression may facilitate clinical screening of patients sensitive to anti-HER2-targeted therapy.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shanghai

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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