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伊朗结直肠癌患者骨形态发生蛋白3甲基化的评估

Assessment of Bone Morphogenetic Protein 3 Methylation in Iranian Patients with Colorectal Cancer.

作者信息

Houshmand Massoud, Abbaszadegan Mohammad Reza, Kerachian Mohammad Amin

机构信息

Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Middle East J Dig Dis. 2017 Jul;9(3):158-163. doi: 10.15171/mejdd.2017.67.

DOI:10.15171/mejdd.2017.67
PMID:28894518
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5585908/
Abstract

BACKGROUND Colorectal cancer (CRC) is a common cancer that results in outstanding morbidity and mortality worldwide. DNA methylation is one of the most important epigenetic events that is thought to occur during the early stages of oncogenic transformation especially in CRC. The aim of this study was to investigate whether hypermethylation of bone morphogenetic protein 3 (BMP3) in tissue samples is implicated in Iranian patients with CRC. METHODS From fresh frozen tissue samples of 30 patients with CRC, the DNA was isolated, treated with sodium bisulfite and analyzed by methylation-specific polymerase chain reaction with primers specific for methylated or unmethylated promoter sequences of the BMP3 gene. Demographic characteristics of the patients including age, sex, tumor grade, location, stage, and TNM classification were evaluated and the relationship between hypermethylation of the gene and clinicopathological features was analyzed. RESULTS Methylation of the BMP3 promoter was often present in the DNA extracted from the tumoral tissues. A sensitivity of 56.66% and specificity of 93.3% were attained in the detection of colorectal neoplasia. CONCLUSION We assumed that solely BMP3 methylation analysis in our population is not sufficient to select the gene as a screening biomarker and it should be considered in combination with other markers to screen for detection of colorectal cancer.

摘要

背景

结直肠癌(CRC)是一种常见癌症,在全球范围内导致显著的发病率和死亡率。DNA甲基化是最重要的表观遗传事件之一,被认为发生在致癌转化的早期阶段,尤其是在结直肠癌中。本研究的目的是调查组织样本中骨形态发生蛋白3(BMP3)的高甲基化是否与伊朗结直肠癌患者有关。方法:从30例结直肠癌患者的新鲜冷冻组织样本中分离DNA,用亚硫酸氢钠处理,并通过甲基化特异性聚合酶链反应,使用针对BMP3基因甲基化或未甲基化启动子序列的特异性引物进行分析。评估患者的人口统计学特征,包括年龄、性别、肿瘤分级、位置、分期和TNM分类,并分析基因高甲基化与临床病理特征之间的关系。结果:BMP3启动子的甲基化经常出现在从肿瘤组织中提取的DNA中。在检测结直肠肿瘤时,灵敏度达到56.66%,特异性达到93.3%。结论:我们认为,仅对我们人群中的BMP3甲基化进行分析不足以将该基因选为筛查生物标志物,应结合其他标志物来筛查结直肠癌的检测。

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引用本文的文献

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Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review.用于早期检测结直肠癌的有前景的表观遗传生物标志物:一项系统综述
Cancers (Basel). 2021 Oct 2;13(19):4965. doi: 10.3390/cancers13194965.
2
DNA methylation markers detected in blood, stool, urine, and tissue in colorectal cancer: a systematic review of paired samples.在结直肠癌的血液、粪便、尿液和组织中检测到的 DNA 甲基化标志物:配对样本的系统评价。
Int J Colorectal Dis. 2021 Feb;36(2):239-251. doi: 10.1007/s00384-020-03757-x. Epub 2020 Oct 6.
3
BMP3 promoter hypermethylation in plasma-derived cell-free DNA in colorectal cancer patients.

本文引用的文献

1
Detection of methylated septin 9 in tissue and plasma of colorectal patients with neoplasia and the relationship to the amount of circulating cell-free DNA.结直肠癌瘤变患者组织和血浆中甲基化septin 9的检测及其与循环游离DNA量的关系
PLoS One. 2014 Dec 19;9(12):e115415. doi: 10.1371/journal.pone.0115415. eCollection 2014.
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Adenoma detection rates in an opportunistic screening colonoscopy program in Iran, a country with rising colorectal cancer incidence.在伊朗这个结直肠癌发病率不断上升的国家,一项机会性筛查结肠镜检查项目中的腺瘤检出率。
BMC Gastroenterol. 2014 Nov 18;14:196. doi: 10.1186/s12876-014-0196-8.
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Methylated Bone Morphogenetic Protein 3 (BMP3) Gene: Evaluation of Tumor Suppressor Function and Biomarker Potential in Biliary Cancer.
结直肠癌患者血浆游离DNA中BMP3启动子的高甲基化
Genes Genomics. 2018 Apr;40(4):423-428. doi: 10.1007/s13258-017-0644-2. Epub 2018 Jan 10.
甲基化骨形态发生蛋白3(BMP3)基因:胆管癌中肿瘤抑制功能及生物标志物潜力评估
J Mol Biomark Diagn. 2013 Aug 3;4(145):1000145. doi: 10.4172/2155-9929.1000145.
4
The CpG island methylator phenotype (CIMP) in colorectal cancer.结直肠癌中的CpG岛甲基化表型(CIMP)
Gastroenterol Hepatol Bed Bench. 2013 Summer;6(3):120-8.
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The molecular genetics of colorectal cancer.结直肠癌的分子遗传学
Frontline Gastroenterol. 2014 Jan;5(1):26-30. doi: 10.1136/flgastro-2013-100329. Epub 2013 Aug 21.
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Clinical applications of DNA methylation biomarkers in colorectal cancer.DNA甲基化生物标志物在结直肠癌中的临床应用
Epigenomics. 2013 Apr;5(2):105-8. doi: 10.2217/epi.13.4.
7
Serum-based DNA methylation biomarkers in colorectal cancer: potential for screening and early detection.基于血清的结直肠癌 DNA 甲基化生物标志物:筛查和早期检测的潜力。
J Cancer. 2013;4(3):210-6. doi: 10.7150/jca.5839. Epub 2013 Mar 1.
8
Colorectal cancer screening: Time for action in Iran.结直肠癌筛查:伊朗行动之时。
World J Gastrointest Oncol. 2012 Apr 15;4(4):82-3. doi: 10.4251/wjgo.v4.i4.82.
9
Quantification of methylated markers with a multiplex methylation-specific technology.采用多重甲基化特异性技术进行甲基化标记物的定量分析。
Clin Chem. 2012 Feb;58(2):375-83. doi: 10.1373/clinchem.2011.171264. Epub 2011 Dec 22.
10
CpG island methylation in colorectal cancer: past, present and future.结直肠癌中的CpG岛甲基化:过去、现在与未来
Patholog Res Int. 2011 Apr 12;2011:902674. doi: 10.4061/2011/902674.