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甲状腺乳头状癌中的表观遗传修饰及其对临床病理特征的影响。

The Epigenetic Modification of in Papillary Thyroid Carcinoma and its Effects on Clinic-Pathological Features.

作者信息

Sheikholeslami Sara, Azizi Fereidoun, Ghasemi Asghar, Alibakhshi Abbas, Parsa Hossein, Shivaee Setareh, Zarif-Yeganeh Marjan, Hedayati Mehdi, Teimoori-Toolabi Ladan

机构信息

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

Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Public Health. 2022 Mar;51(3):634-642. doi: 10.18502/ijph.v51i3.8940.

Abstract

BACKGROUND

Epigenetic alterations such as DNA methylation are known as the main cause of different types of cancers through inactivation of tumor suppressor genes, especially thyroid cancer. Identification of novel and effective markers are important in diagnosis and prevention of thyroid cancer. In the present study, the expression and methylation of Solute carrier family 5 member 8 () in Papillary Thyroid Carcinoma (PTC) in comparison to multinodular goiter (MNG) have been studied.

METHODS

Overall, 41 patients with PTC and 36 patients affected by MNG were recruited from four hospitals in Tehran and Qazvin, Iran in 2018. Thyroid tissues were obtained during thyroidectomy. RNA and DNA were extracted from thyroid tissues. Quantitative RT-PCR assay was performed for determining the mRNA level of while Methylation-Sensitive High-Resolution Methylation was applied for assessing the methylation status.

RESULTS

Methylation status of three regions composed of 52 CpG islands in the promoter of gene was studied by HRM assay. level in PTC tissues was significantly downregulated in average 0.4 fold in comparison with MNG tissues (=0.05). The aberrant methylation of (b) region was remarkably different in PTC and MNG cases. The promoter methylation of (c) was significantly related to mutations and vascular invasion in PTC patients.

CONCLUSION

The aberrant promoter hyper methylation of SLC5A8 was related to aggressive PTC. Therefore, there is some evidence to support the hypothesis that could be a paly important role in the development of PTC.

摘要

背景

DNA甲基化等表观遗传改变是多种癌症的主要病因,可导致肿瘤抑制基因失活,甲状腺癌尤其如此。鉴定新的有效标志物对甲状腺癌的诊断和预防至关重要。在本研究中,我们比较了甲状腺乳头状癌(PTC)和结节性甲状腺肿(MNG)中溶质载体家族5成员8(SLC5A8)的表达和甲基化情况。

方法

2018年,我们从伊朗德黑兰和加兹温的四家医院招募了41例PTC患者和36例MNG患者。在甲状腺切除术中获取甲状腺组织。从甲状腺组织中提取RNA和DNA。采用定量逆转录聚合酶链反应(RT-PCR)测定SLC5A8的mRNA水平,同时应用甲基化敏感高分辨率熔解曲线分析(MS-HRM)评估甲基化状态。

结果

通过HRM分析研究了SLC5A8基因启动子中由52个CpG岛组成的三个区域的甲基化状态。与MNG组织相比,PTC组织中SLC5A8水平平均显著下调0.4倍(P=0.05)。PTC和MNG病例中SLC5A8(b)区域的异常甲基化有显著差异。PTC患者中SLC5A8(c)区域的启动子甲基化与BRAF突变和血管侵犯显著相关。

结论

SLC5A8启动子异常高甲基化与侵袭性PTC有关。因此,有证据支持SLC5A8可能在PTC发生发展中起重要作用这一假说。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/265f/9276613/fb5808a3f792/IJPH-51-634-g001.jpg

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