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对 RET 阳性和 RET 阴性甲状腺髓样癌患者血浆样本中包括 miR-144 和 miR-34a 在内的 miRNAs 表达的研究。

An investigation on the expression of miRNAs including miR-144 and miR-34a in plasma samples of RET-positive and RET-negative medullar thyroid carcinoma patients.

机构信息

Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Cellular and Molecular Endocrine Research Center (CMERC), Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Cell Physiol. 2020 Feb;235(2):1366-1373. doi: 10.1002/jcp.29055. Epub 2019 Jul 11.

DOI:10.1002/jcp.29055
PMID:31297834
Abstract

Medullary thyroid carcinoma (MTC) is a scarce cancerous disease, originating from parafollicular C cells of the thyroid gland. MTC can be manifested as an aggressive carcinoma with metastasis, especially in sporadic forms. Mutations of the rearranged during transfection (RET) proto-oncogene occurs in all hereditary and a few somatic MTCs, so detection of RET mutations is needed for prompt and appropriate treatment. MicroRNAs (miRNAs) are noncoding regulatory RNAs. Extensive studies have done in progress or suppression of several types of cancers such as MTCs with the remarkable application as prognostic markers. Of the effective miRNAs in cancers, miR-144 and miR-34 were evaluated in our study. Blood samples of 25 RET-positive and 25 RET-negative blood samples of patients with MTC were evaluated for these miRNAs, using quantitative real-time polymerase chain reaction (RT-qPCR). Analysis of the results was performed by the 2 method, showing that miR-144 and miR-34a expression had a relative increase in patients with MTC compared with normal control samples and also in RET positives versus RET negatives. We recruited 50 out of 350 MTC plasma samples (27 female and 23 male) which were selected based on RET mutation in exon 11 (25 RET-positive and 25 RET-negative), with a mean ± SD age of 37.04 ± 1.74 years. Receiver operating characteristic (ROC) curve analysis was done to investigate the prognostic value of these miRNAs; although, they showed no significant prognostic value as MTC biomarkers in plasma samples. In conclusion, miRNAs can be used as biomarkers of cancers such as MTC; however, more studies are needed to find the best candidate miRNAs for the diagnosis of cancers.

摘要

甲状腺髓样癌(MTC)是一种罕见的癌症,起源于甲状腺滤泡旁 C 细胞。MTC 可以表现为具有转移的侵袭性癌,尤其是在散发性形式中。重排过程中易位(RET)原癌基因的突变发生在所有遗传性和少数体细胞 MTC 中,因此需要检测 RET 突变以进行及时和适当的治疗。微小 RNA(miRNA)是一类非编码调节 RNA。大量研究正在进行或抑制几种类型的癌症,如 MTC,作为预后标志物具有显著的应用。在癌症中,miR-144 和 miR-34 是有效的 miRNA,我们在研究中对其进行了评估。使用定量实时聚合酶链反应(RT-qPCR)评估了 25 例 RET 阳性和 25 例 RET 阴性 MTC 患者的血液样本中的这些 miRNA。通过 2 方法分析结果,结果表明与正常对照样本相比,MTC 患者的 miR-144 和 miR-34a 表达相对增加,且在 RET 阳性与 RET 阴性之间也存在差异。我们从 350 例 MTC 血浆样本中招募了 50 例(27 名女性和 23 名男性),这些样本是根据外显子 11(25 例 RET 阳性和 25 例 RET 阴性)中的 RET 突变选择的,平均年龄为 37.04±1.74 岁。进行了受试者工作特征(ROC)曲线分析,以研究这些 miRNA 的预后价值;然而,它们在血浆样本中作为 MTC 生物标志物并没有显示出显著的预后价值。总之,miRNA 可以作为癌症的生物标志物,如 MTC;然而,需要进一步研究以找到诊断癌症的最佳候选 miRNA。

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