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在几种肿瘤中,外周血的整体 DNA 低甲基化程度与匹配的肿瘤组织中的程度相关。

The degree of global DNA hypomethylation in peripheral blood correlates with that in matched tumor tissues in several neoplasia.

机构信息

Department of Neurosurgery and Neurotraumatology, Karol Marcinkowski University of Medical Sciences, Poznan, Poland.

Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznan, Poland.

出版信息

PLoS One. 2014 Mar 20;9(3):e92599. doi: 10.1371/journal.pone.0092599. eCollection 2014.

Abstract

There are no good blood and serum biomarkers for detection, follow up, or prognosis of brain tumors. However, they are needed for more detailed tumor classification, better prognosis estimation and selection of an efficient therapeutic strategy. The aim of this study was to use the epigenetic changes in DNA of peripheral blood samples as a molecular marker to diagnose brain tumors as well as other diseases. We have applied a very precise thin-layer chromatography (TLC) analysis of the global amount of 5-methylcytosine (m(5)C) in DNA from brain tumors, colon and breast cancer tissues and peripheral blood samples of the same patients. The m(5)C level in tissue DNA from different brain tumor types, expressed as R coefficient, changes within the range of 0.2-1.6 and overlaps with R of that of blood samples. It negatively correlates with the WHO malignancy grade. The global DNA hypomethylation quantitative measure in blood, demonstrates a big potential for development of non-invasive applications for detection of a low and a high grade brain tumors. We have also used this approach to analyze patients with breast and colon cancers. In all these cases the m(5)C amount in DNA cancer tissue match with data of blood. This study is the first to demonstrate the potential role of global m(5)C content in blood DNA for early detection of brain tumors and others diseases. So, genomic DNA hypomethylation is a promising marker for prognosis of various neoplasms as well as other pathologies.

摘要

目前,还没有用于检测、随访或预测脑肿瘤的良好血液和血清生物标志物。然而,为了更详细地进行肿瘤分类、更准确地估计预后并选择有效的治疗策略,这些标志物是非常必要的。本研究旨在利用外周血样本中 DNA 的表观遗传变化作为分子标志物,诊断脑肿瘤以及其他疾病。我们应用非常精确的薄层色谱(TLC)分析方法,检测了脑肿瘤、结肠癌和乳腺癌组织以及同一患者外周血样本中 DNA 的 5-甲基胞嘧啶(m(5)C)总量。不同脑肿瘤类型组织 DNA 中的 m(5)C 水平,以 R 系数表示,变化范围在 0.2-1.6 之间,与血液样本的 R 值重叠。它与 WHO 恶性程度呈负相关。血液中全基因组 DNA 低甲基化的定量测量显示出了巨大的潜力,可用于开发用于检测低级别和高级别脑肿瘤的非侵入性应用。我们还使用这种方法分析了乳腺癌和结肠癌患者。在所有这些情况下,肿瘤组织中 DNA 的 m(5)C 含量都与血液数据相匹配。本研究首次证明了血液 DNA 中全基因组 m(5)C 含量在早期检测脑肿瘤和其他疾病方面的潜在作用。因此,基因组 DNA 低甲基化是预测各种肿瘤以及其他病理情况的有前途的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9b5/3961436/3dd9c7b9a202/pone.0092599.g001.jpg

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