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BRAF 突变、选定的 microRNA 和基因在原发性甲状腺乳头状癌及其局部淋巴结转移中的表达。

BRAF mutation, selected miRNAs and genes expression in primary papillary thyroid carcinomas and local lymph node metastases.

机构信息

Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Motol, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.

Department of Biology, Faculty of Medicine in Pilsen, Charles University, Pilsen 32300, Czech Republic.

出版信息

Pathol Res Pract. 2024 Jun;258:155319. doi: 10.1016/j.prp.2024.155319. Epub 2024 Apr 23.

Abstract

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

摘要

在肿瘤发生过程中,癌症相关基因的突变伴随着表观遗传事件,通过调节通路和涉及病理生物学的基因表达的修饰。这种癌症相关的突变、miRNA 和基因表达可能是最常见的甲状腺乳头状癌(PTC)的有前途的分子标志物。然而,关于它们之间关系的研究数据有限。本研究旨在分析 BRAF 突变、选定的 microRNAs(miR-21、miR-34a、miR-146b 和 miR-9)与参与 PTC 发病机制的选定基因(LGALS3、NKX2-1、TACSTD2、TPO)的表达之间的相互作用。研究队列包括 60 例原发性甲状腺乳头状癌(PTC),分为经典型(PTC/C;n=50)和侵袭性滤泡变体型(PTC/F;n=10),以及 40 对淋巴结转移(LNM)。在原发性和复发性/持续性甲状腺乳头状癌中确定 BRAF 突变状态。将突变结果与原发性和转移性癌组织之间进行比较,以及与原发性 PTC 中的选定基因和 miRNA 表达之间进行比较。此外,分别比较原发性 PTC 与非肿瘤组织以及局部淋巴结转移性肿瘤之间的 miRNA 和基因表达。所有研究的标志物均显示出几种显著的相互作用和关系。总之,据我们所知,这是首次对 BRAF 突变状态、原发性 PTC 中选定基因和 miRNA 的 mRNA 表达水平以及配对的 LNM 进行综合研究。

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