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miR-21 作为曲妥珠单抗治疗人表皮生长因子受体 2 阳性转移性乳腺癌的预测和预后因素。

MicroRNA-21 as a predictor and prognostic factor for trastuzumab therapy in human epidermal growth factor receptor 2-positive metastatic breast cancer.

机构信息

Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

出版信息

J Cell Biochem. 2019 Mar;120(3):3459-3466. doi: 10.1002/jcb.27620. Epub 2018 Sep 23.

Abstract

Breast cancer is the second most common cancer diagnosed worldwide. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents about 20% to 30% of all breast cancers. Trastuzumab is used in the treatment of HER2-positive breast cancer. MicroRNA-21 (miR-21) is an oncomiR that acts by inhibiting many tumor-suppressor genes. We analyzed the relative expression levels of serum miR-21 in 20 HER2-positive metastatic breast cancer patients before and after 3 months of treatment with trastuzumab. miR-21 levels decreased with a high significant difference after trastuzumab therapy (P = 0.001). Although miR-21 expression levels were lower in responders than in nonresponders, the difference was not statistically significant ( P = 0.6). Our results demonstrated a significant negative correlation between its basal expression, expression levels after treatment, and time to progression ( P = 0.03 and 0.01, respectively). These results make miR-21 a potential prognostic factor for HER2-positive metastatic breast cancer patients. Additionally, it can be an interesting potential target in therapy using antisense oligonucleotides for miR-21.

摘要

乳腺癌是全球第二大常见癌症。人表皮生长因子受体 2(HER2)阳性乳腺癌约占所有乳腺癌的 20%至 30%。曲妥珠单抗用于治疗 HER2 阳性乳腺癌。microRNA-21(miR-21)是一种致癌 miRNA,通过抑制许多肿瘤抑制基因发挥作用。我们分析了 20 例 HER2 阳性转移性乳腺癌患者在接受曲妥珠单抗治疗前 3 个月和治疗后的血清 miR-21 的相对表达水平。曲妥珠单抗治疗后 miR-21 水平显著降低(P=0.001)。尽管应答者的 miR-21 表达水平低于无应答者,但差异无统计学意义(P=0.6)。我们的结果表明,其基础表达水平、治疗后表达水平与进展时间之间存在显著负相关(P=0.03 和 0.01)。这些结果表明,miR-21 可能是 HER2 阳性转移性乳腺癌患者的潜在预后因素。此外,它可能是一种有趣的潜在治疗靶点,可使用针对 miR-21 的反义寡核苷酸。

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