儿童星形细胞瘤中TPT1通路的多态性。

IF 3.9 4区 医学 Q2 NEUROSCIENCES ASN NEURO Pub Date : 2023-01-01 DOI:10.1177/17590914231153481
Eduardo Morais de Castro, Leonardo Vinícius Barbosa, Aline Simoneti Fonseca, Seigo Nagashima, Caroline Busatta Vaz de Paula, Rafaela Zeni, Letícia Arianne Panini do Carmo, Luciane R Cavalli, Luiz Fernando Bleggi Torres, Andrea Senff Ribeiro, Lucia de Noronha, Cleber Machado-Souza
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引用次数: 0

摘要

中枢神经系统肿瘤,尤其是星形细胞瘤,是儿童期发病率和死亡率最高的实体肿瘤。诊断是基于组织病理学特征,但分子方法已越来越多地使用。翻译控制肿瘤蛋白(translation - controlled tumor protein, TCTP)是由肿瘤蛋白翻译控制1 (translation - controlled 1, TPT1)基因编码的一种多功能蛋白,在细胞周期中具有重要的生理作用。该蛋白的表达与几种肿瘤有关,包括成人的星形细胞瘤。然而,这种蛋白在儿童星形细胞瘤中的作用在很大程度上是未知的。我们的目的是评估在儿童星形细胞瘤病例中,在福尔马林固定石蜡包埋(FFPE)样本中,TPT1基因和其他与其分子通路相关的基因(如MTOR、MDM2、TP53和CDKN1A)的多态性频率,以及其与蛋白质表达和临床变量的相关性。这些样本进行基因分型和免疫组织化学分析。最具揭示性的结果是MDM2基因rs117039649 [G/C],其中C多态性等位基因仅在胶质母细胞瘤中存在(p = 0.028)。CDKN1A基因rs3176334 [T/C]仅在高级别星形细胞瘤中呈现纯合多态性基因型(p = 0.039)。胶质母细胞瘤患者细胞质MDM2的免疫组织化学表达与更高的生存率相关(p = 0.018)。MDM2和CDKN1A基因多态性的存在,以及MDM2表达之间的特定相关性,表明可能与儿童星形细胞瘤的风险相关。本研究寻求TCTP通路和相关蛋白在儿童星形细胞瘤发生中的可能作用,其中一些可能作为这些患者的预后标志物具有潜在影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Polymorphisms in TPT1 Pathways in Pediatric Astrocytomas.

Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 (TPT1) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR, MDM2, TP53, and CDKN1A, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas (p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared (p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma (p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.

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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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