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miR-155、miR-15a 和 miR-19a 在乳腺癌患者外周血中的表达水平:细胞固有放射敏感性的可能生物标志物。

Expression level of miR-155, miR-15a and miR-19a in peripheral blood of ductal carcinoma breast cancer patients: Possible bioindicators for cellular inherent radiosensitivity.

机构信息

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Exp Mol Pathol. 2022 Jun;126:104758. doi: 10.1016/j.yexmp.2022.104758. Epub 2022 Mar 23.

Abstract

Examination of cellular radiosensitivity (RS) helps prevent the adverse side-effects of radiotherapy in radioresistant tumors. We aim to study whether miRNA-155 (miR-155), miR-19a and miR-15a can predict inherent RS according to cellular RS in breast cancer (BC) patients. This study was done on the blood samples of 40 invasive ductal carcinoma (IDC) BC patients and 15 healthy women. G2 assay was performed to evaluate cellular RS. To study the expression level of these miRNAs in blood, qRT-PCR was used. The sensitivity and specificity of the studied miRNAs were assessed by the receiver operating characteristic (ROC) curve. The yield of spontaneous (SY) and radiation-induced (RIY) chromatid breaks (CBs) was significantly different between control and patient groups (p < 0.0001). A cut-off value was specified to recognize the patients with cellular RS from those without. Expression of miR-15a was significantly downregulated (p < 0.0001) in BC patients. However, miR-19a showed upregulation in the blood of BC patients. It was also found the expression level of miR-155 and miR-19a were significantly associated with frequency of CBs (FCB) (p < 0.05). ROC curve analysis manifested that the miR-15a and miR-19a differentiate BC patients and healthy women with 0.91 and 0.68 yielding an area under the ROC curve, respectively. miR-155 and miR-19a discriminate between BC patients with and without cellular RS with area under the ROC curve 0.98 and 0.68. Our findings uncovered miR-155 and miR-19a could be applied as a bioindicator to predict cellular radiosensitivity of BC patients.

摘要

细胞放射敏感性 (RS) 的检查有助于预防放射抗拒肿瘤的放疗不良反应。我们旨在研究微小 RNA-155 (miR-155)、miR-19a 和 miR-15a 是否可以根据乳腺癌 (BC) 患者的细胞 RS 预测固有 RS。本研究在 40 例浸润性导管癌 (IDC) BC 患者和 15 名健康女性的血液样本上进行。G2 测定法用于评估细胞 RS。为了研究这些 miRNA 在血液中的表达水平,使用了 qRT-PCR。通过接受者操作特征 (ROC) 曲线评估了研究 miRNA 的敏感性和特异性。自发 (SY) 和辐射诱导 (RIY) 染色单体断裂 (CB) 的产率在对照组和患者组之间有显著差异 (p < 0.0001)。指定了一个截止值来识别具有细胞 RS 的患者和不具有细胞 RS 的患者。miR-15a 在 BC 患者中的表达显著下调 (p < 0.0001)。然而,miR-19a 在 BC 患者的血液中上调。还发现 miR-155 和 miR-19a 的表达水平与 CB 频率 (FCB) 显著相关 (p < 0.05)。ROC 曲线分析表明,miR-15a 和 miR-19a 可分别以 0.91 和 0.68 的ROC 曲线下面积将 BC 患者与健康女性区分开来。miR-155 和 miR-19a 以 0.98 和 0.68 的ROC 曲线下面积区分 BC 患者是否具有细胞 RS。我们的研究结果表明,miR-155 和 miR-19a 可以作为生物标志物应用于预测 BC 患者的细胞放射敏感性。

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