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组蛋白乙酰转移酶 1 在预后不良、高级脑膜和神经胶质瘤中的过度表达:免疫组化和适配体组化研究。

Histone Acetyl Transferase 1 Is Overexpressed in Poor Prognosis, High-grade Meningeal and Glial Brain Cancers: Immunohistochemical and Aptahistochemical Study.

机构信息

Cell Biology and Genetics, Department of Biomedicine and Biotechnology, University of Alcalá, Alcalá de Henares, Spain.

Laboratory Medicine Department, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain.

出版信息

J Histochem Cytochem. 2024 Aug-Sep;72(8-9):585-599. doi: 10.1369/00221554241272341. Epub 2024 Aug 24.

Abstract

Primary malignancies of the central nervous system account for 2% of all cancers in adults and almost 15% in children under 15 years of age. The prognosis of brain anaplastic cancers and glioblastomas remains extremely poor, with devastating survival expectative, and new molecular markers and therapeutic targets are essential. Epigenetic changes constitute an extensive field for the development of new diagnostic and therapeutic strategies. Histone acetyl transferase-1 (HAT1) has merged as a potential prognostic marker and therapy target for different malignancies. Data repository analysis showed HAT1 mRNA overexpression in gliomas and has been described its alternative splicing in glioblastomas. Using immunohistochemical and aptahistochemical methods, we analyzed the expression of HAT1 in meningiomas, oligodendrogliomas, and astroglial cancers. We observed that HAT1 overexpression is associated with the most aggressive tumor types and the worse prognosis, as well as with a higher probability of early relapse in meningiomas. Its cytosolic localization correlates with tumor progression and prognosis. Aptamers, synthetic oligonucleotides capable to bind and inhibit a wide variety of targets, are considered as promising diagnostic and therapeutic tools. Aptahistochemistry using the aptamer apHAT610 offered superior results in comparison with the antibody used, as a good example of the potential of aptamers as diagnostic tools for histopathology.

摘要

原发性中枢神经系统肿瘤占成人所有癌症的 2%,占 15 岁以下儿童癌症的近 15%。脑间变性癌和胶质母细胞瘤的预后仍然非常差,生存预期令人沮丧,因此需要新的分子标志物和治疗靶点。表观遗传改变是开发新的诊断和治疗策略的一个广泛领域。组蛋白乙酰转移酶-1(HAT1)已成为不同恶性肿瘤的潜在预后标志物和治疗靶点。数据分析显示,HAT1 在神经胶质瘤中存在 mRNA 过表达,并已描述其在胶质母细胞瘤中的选择性剪接。我们使用免疫组织化学和适体组织化学方法分析了 HAT1 在脑膜瘤、少突胶质细胞瘤和星形细胞瘤中的表达。我们观察到 HAT1 的过表达与最具侵袭性的肿瘤类型和最差的预后相关,并且在脑膜瘤中更早复发的可能性更高。其细胞溶质定位与肿瘤进展和预后相关。适体是能够结合和抑制多种靶标的合成寡核苷酸,被认为是有前途的诊断和治疗工具。与使用的抗体相比,使用适体 apHAT610 进行适体组织化学的结果更好,这是适体作为组织病理学诊断工具的潜力的一个很好的例子。

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