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