MNX1 Promotes Anti-HER2 Therapy Sensitivity via Transcriptional Regulation of CD-M6PR in HER2-Positive Breast Cancer.
MNX1 Promotes Anti-HER2 Therapy Sensitivity via Transcriptional Regulation of CD-M6PR in HER2-Positive Breast Cancer.
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MNX1在her2阳性乳腺癌中通过CD-M6PR的转录调控促进抗her2治疗敏感性。
DOI：
10.3390/ijms25010221
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发表时间：
2023-12-22
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
虽然针对人表皮生长因子受体2 （HER2）阳性乳腺癌的靶向治疗显著延长了患者的生存时间，改善了患者的生活质量，但耐药性也逐渐出现。本研究探讨了运动神经元和胰腺同源盒1 （MNX1）基因对her2阳性乳腺癌药物敏感性影响的机制。2017年7月至2018年7月，收集本中心接受紫杉醇、卡铂和曲妥珠单抗新辅助治疗的her2阳性乳腺癌患者的核心针活检。根据治疗效果将81例患者分为病理完全缓解（pCR）组和非pCR组。高通量RNA测序结果与GSE181574数据集一起进行分析。两个测序数据集中，MNX1在pCR组均较非pCR组显著上调，提示MNX1可能与her2阳性乳腺癌的药物敏感性相关。同时，组织阵列结果显示，MNX1高表达与预后良好相关。体外功能试验显示，上调MNX1可显著提高her2阳性乳腺癌细胞对拉帕替尼和吡罗替尼的敏感性。综上所述，MNX1可能作为her2阳性乳腺癌患者的预后标志物，其表达可能有助于临床筛选对抗her2靶向治疗敏感的患者。
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.
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针对早期 HER2 阳性乳腺癌的个性化治疗。
DOI：
10.1038/s41571-019-0299-9
发表时间：
2020-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Goutsouliak K;Veeraraghavan J;Sethunath V;De Angelis C;Osborne CK;Rimawi MF;Schiff R
通讯作者：
Schiff R
影响因子：
5.7
作者：
Ogitani Y;Hagihara K;Oitate M;Naito H;Agatsuma T
通讯作者：
Agatsuma T
影响因子：
50.3
作者：
Sun Y;Zhou B;Mao F;Xu J;Miao H;Zou Z;Phuc Khoa LT;Jang Y;Cai S;Witkin M;Koche R;Ge K;Dressler GR;Levine RL;Armstrong SA;Dou Y;Hess JL
通讯作者：
Hess JL
影响因子：
5.3
作者：
Pedersen, Kim;Angelini, Pier-Davide;Arribas, Joaquin
通讯作者：
Arribas, Joaquin
影响因子：
15.9
作者：
Gilbert, Penney M.;Mouw, Janna K.;Weaver, Valerie M.
通讯作者：
Weaver, Valerie M.