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miR-200c/FOXP3 网络:预测曲妥珠单抗治疗 HER2 阳性乳腺癌反应的有前途的生物标志物。

The MiR-200c/FOXP3 Network: A Promising Biomarker for Predicting Trastuzumab Response in HER2-Positive Breast Cancer.

机构信息

Department of Biochemistry, College of Medicine, University of Ha'il, Ha'il, Saudi Arabia.

College of Medicine, University of Ha'il, Ha'il, Saudi Arabia.

出版信息

Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241292226. doi: 10.1177/15330338241292226.

Abstract

Resistance to Trastuzumab is a significant challenge in the management of HER2-positive Metastatic Breast cancer (HER2-MBC), and a better understanding of the molecular causes of resistance is required to develop more effective treatment plans. While elevated plasma levels of miR-200 and FOXP3 have been linked to breast cancer progression and treatment response, no clinical studies have confirmed these results. The study involved 40 patients with HER2-positive metastatic breast cancer (HER2-MBC). The expression levels of miR-200c-3p and the FOXP3 gene were assessed in plasma samples at two time points: baseline (BL) and after the consent completion of one cycle of Trastuzumab, utilizing quantitative polymerase chain reaction (qPCR). Clinical response to Trastuzumab was evaluated 12 months post-therapy and correlated with the time to progression (TTP) through Kaplan-Meier analysis. Low plasma expression level of miR-200c-3p was detected before therapy in HER2-MBC, compared to healthy controls, and decreased dramatically in the follow-up sample at disease progression, while increased after one cycle of Trastuzumab therapy in patients who were sensitive to Trastuzumab. At baseline, a low expression level of miR-200c was significantly associated with overexpression of FOXP3, poor prognosis, and shorter time to progression. The findings suggest that miR-200c-3p may be a promising biomarker for predicting the response to Trastuzumab in HER2-MBC patients.

摘要

曲妥珠单抗耐药是治疗人表皮生长因子受体 2(HER2)阳性转移性乳腺癌(HER2-MBC)的重大挑战,需要更好地了解耐药的分子原因,以制定更有效的治疗方案。虽然循环中 miR-200 和 FOXP3 水平升高与乳腺癌的进展和治疗反应相关,但尚无临床研究证实这些结果。

该研究纳入了 40 例 HER2 阳性转移性乳腺癌(HER2-MBC)患者。采用实时定量聚合酶链反应(qPCR)技术,分别在基线(BL)和曲妥珠单抗治疗 1 个周期完成后评估血浆样本中 miR-200c-3p 的表达水平和 FOXP3 基因的表达水平。治疗 12 个月后评估患者对曲妥珠单抗的临床反应,并通过 Kaplan-Meier 分析与无进展生存期(TTP)进行相关性分析。

与健康对照组相比,HER2-MBC 患者在治疗前的血浆中 miR-200c-3p 表达水平较低,在疾病进展的随访样本中显著降低,而在对曲妥珠单抗敏感的患者中,在接受曲妥珠单抗治疗 1 个周期后表达水平显著升高。在基线时,miR-200c 的低表达水平与 FOXP3 的过表达、预后不良和 TTP 缩短显著相关。

这些发现表明,miR-200c-3p 可能是预测 HER2-MBC 患者对曲妥珠单抗反应的有前途的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/118c/11494628/1883c79f4edf/10.1177_15330338241292226-fig1.jpg

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