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[结直肠癌发生过程中游离DNA部分的DNA甲基化改变分析]

[Analysis of DNA methylation alterations in cellfree DNA fraction during colorectal cancer development].

作者信息

Molnár Kinga Barbara

机构信息

Klinikai Orvostudományok Doktori Iskola, Semmelweis Egyetem, Budapest, Hungary.

出版信息

Magy Onkol. 2020 Mar 17;64(1):70-72. Epub 2019 Nov 21.

PMID:32181765
Abstract

During colorectal cancer (CRC) development, in addition to genetic alterations, several epigenetic changes, including DNA methylation in the promoter regions accumulate in tumor cells. Cell-free DNA (cfDNA) in the circulatory system can originate also from tumor tissue; therefore the evaluation of methylated cfDNA in the plasma can be a promising method for early cancer screening. In my Ph.D., I have investigated the rate of cfDNA's release and stability using animal models. I aimed to compile an epigenetic marker panel, which contains genes with altered DNA methylation patterns in the healthy-colorectal adenoma-cancer sequence. I have found that the methylation level of SFRP1, SFRP2, SDC2, and PRIMA1 gene promoters has already increased in adenoma stages in both tissue and plasma samples. Immunohistochemistry analyses indicated decreasing protein expression in parallel with elevated methylation. According to our results, cfDNA amount and the methylation have been influenced by DNA isolation and blood collection methods.

摘要

在结直肠癌(CRC)发生发展过程中,除了基因改变外,肿瘤细胞还会积累多种表观遗传变化,包括启动子区域的DNA甲基化。循环系统中的游离DNA(cfDNA)也可源自肿瘤组织;因此,评估血浆中甲基化的cfDNA可能是一种很有前景的早期癌症筛查方法。在我的博士研究中,我使用动物模型研究了cfDNA的释放速率和稳定性。我的目标是编制一个表观遗传标记物面板,其中包含在健康-结直肠腺瘤-癌序列中DNA甲基化模式发生改变的基因。我发现,在腺瘤阶段,组织和血浆样本中SFRP1、SFRP2、SDC2和PRIMA1基因启动子的甲基化水平均已升高。免疫组织化学分析表明,蛋白质表达随着甲基化水平升高而降低。根据我们的结果,cfDNA的量和甲基化受到DNA分离和血液采集方法的影响。

相似文献

1
[Analysis of DNA methylation alterations in cellfree DNA fraction during colorectal cancer development].[结直肠癌发生过程中游离DNA部分的DNA甲基化改变分析]
Magy Onkol. 2020 Mar 17;64(1):70-72. Epub 2019 Nov 21.
2
Colorectal adenoma and cancer detection based on altered methylation pattern of SFRP1, SFRP2, SDC2, and PRIMA1 in plasma samples.基于 SFRP1、SFRP2、SDC2 和 PRIMA1 血浆样本中甲基化模式改变对结直肠腺瘤和癌症的检测。
Epigenetics. 2017 Sep;12(9):751-763. doi: 10.1080/15592294.2017.1356957. Epub 2017 Sep 26.
3
Aging related methylation influences the gene expression of key control genes in colorectal cancer and adenoma.衰老相关的甲基化影响结直肠癌和腺瘤中关键调控基因的基因表达。
World J Gastroenterol. 2016 Dec 21;22(47):10325-10340. doi: 10.3748/wjg.v22.i47.10325.
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[Characteristics and diagnostic applications of circulating cell-free DNA in colorectal cancer].[循环游离DNA在结直肠癌中的特征及诊断应用]
Orv Hetil. 2019 Jul;160(30):1167-1177. doi: 10.1556/650.2019.31486.
5
Blood Collection and Cell-Free DNA Isolation Methods Influence the Sensitivity of Liquid Biopsy Analysis for Colorectal Cancer Detection.血液采集和游离 DNA 分离方法影响液体活检分析结直肠癌检测的灵敏度。
Pathol Oncol Res. 2019 Jul;25(3):915-923. doi: 10.1007/s12253-018-0382-z. Epub 2018 Jan 27.
6
DNA hypermethylation and decreased mRNA expression of MAL, PRIMA1, PTGDR and SFRP1 in colorectal adenoma and cancer.结直肠腺瘤和癌中 MAL、PRIMA1、PTGDR 和 SFRP1 的 DNA 高甲基化及 mRNA 表达降低
BMC Cancer. 2015 Oct 19;15:736. doi: 10.1186/s12885-015-1687-x.
7
A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples.一种新方法,通过对汇集样本中的循环无细胞游离 DNA 进行全基因组范围内的表观遗传组学发现,以开发用于结直肠癌筛查的非侵入性甲基化生物标志物。
Clin Epigenetics. 2018 Apr 16;10:53. doi: 10.1186/s13148-018-0487-y. eCollection 2018.
8
Diagnostic and prognostic role of cell-free DNA testing for colorectal cancer patients.循环游离 DNA 检测在结直肠癌患者中的诊断和预后作用。
Int J Cancer. 2017 Apr 15;140(8):1888-1898. doi: 10.1002/ijc.30565. Epub 2017 Jan 5.
9
Circadian Rhythm of Methylated Septin 9, Cell-Free DNA Amount and Tumor Markers in Colorectal Cancer Patients.结直肠癌患者甲基化丝聚蛋白9、游离DNA含量及肿瘤标志物的昼夜节律
Pathol Oncol Res. 2017 Jul;23(3):699-706. doi: 10.1007/s12253-016-0174-2. Epub 2016 Dec 30.
10
Discovery of methylated circulating DNA biomarkers for comprehensive non-invasive monitoring of treatment response in metastatic colorectal cancer.发现甲基化循环 DNA 生物标志物,用于转移性结直肠癌的全面无创治疗反应监测。
Gut. 2018 Nov;67(11):1995-2005. doi: 10.1136/gutjnl-2016-313372. Epub 2017 Oct 5.

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Sci Rep. 2021 May 11;11(1):9938. doi: 10.1038/s41598-021-89429-4.