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人前列腺组织中APC甲基化水平的焦磷酸测序分析:一种前列腺癌的分子标志物

Pyrosequencing Analysis of APC Methylation Level in Human Prostate Tissues: A Molecular Marker for Prostate Cancer.

作者信息

Yoon Hyung-Yoon, Kim Young-Won, Kang Ho Won, Kim Won Tae, Yun Seok-Joong, Lee Sang-Cheol, Kim Wun-Jae, Kim Yong-June

机构信息

Department of Urology, Chungbuk National University College of Medicine, Cheongju, Korea.

出版信息

Korean J Urol. 2013 Mar;54(3):194-8. doi: 10.4111/kju.2013.54.3.194. Epub 2013 Mar 15.

DOI:10.4111/kju.2013.54.3.194
PMID:23526751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3604574/
Abstract

PURPOSE

Epigenetic alterations such as abnormal DNA methylation are associated with many human cancers. Differences in methylation patterns between neoplastic and normal cells can be used to detect cancer. The aim of the present study was to evaluate the effectiveness of detecting Adenomatous polyposis coli (APC) hypermethylation by quantitative pyrosequencing for discriminating between normal and prostate cancer (PCa) cells and for predicting tumor behaviors.

MATERIALS AND METHODS

A total of 218 human prostate tissues obtained from our institute were assessed: 106 specimens of benign prostatic hyperplasia (BPH) and 112 specimens of PCa. The methylation status of APC was analyzed by quantitative pyrosequencing. The association between the APC methylation level and clinicopathological parameters was explored.

RESULTS

The level of APC methylation was significantly higher in PCa specimens than in BPH specimens (33.3%±20.7% vs. 1.3%±1.8%, p<0.001). The sensitivity and specificity of APC methylation status in discriminating between PCa and BPH reached 89.3% and 98.1%, respectively. Similar results were obtained after stratification by stage, Gleason score, and prostate-specific antigen level. The APC methylation level correlated positively with Gleason score (p trend=0.016). There was no association between the APC methylation level and the PSA level or staging.

CONCLUSIONS

Our results demonstrate that APC methylation is associated with PCa and its aggressive tumor features.

摘要

目的

诸如异常DNA甲基化等表观遗传改变与许多人类癌症相关。肿瘤细胞与正常细胞之间甲基化模式的差异可用于检测癌症。本研究的目的是评估通过定量焦磷酸测序检测腺瘤性息肉病基因(APC)高甲基化在区分正常细胞与前列腺癌细胞以及预测肿瘤行为方面的有效性。

材料与方法

对从本研究所获得的218份人类前列腺组织进行评估:106份良性前列腺增生(BPH)标本和112份前列腺癌(PCa)标本。通过定量焦磷酸测序分析APC的甲基化状态。探讨APC甲基化水平与临床病理参数之间的关联。

结果

PCa标本中APC的甲基化水平显著高于BPH标本(33.3%±20.7%对1.3%±1.8%,p<0.001)。APC甲基化状态在区分PCa和BPH中的敏感性和特异性分别达到89.3%和98.1%。按分期、Gleason评分和前列腺特异性抗原水平分层后获得了相似的结果。APC甲基化水平与Gleason评分呈正相关(p趋势=0.016)。APC甲基化水平与PSA水平或分期之间无关联。

结论

我们的结果表明,APC甲基化与PCa及其侵袭性肿瘤特征相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e117/3604574/b428529cbf79/kju-54-194-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e117/3604574/01b0a16682b3/kju-54-194-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e117/3604574/b428529cbf79/kju-54-194-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e117/3604574/01b0a16682b3/kju-54-194-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e117/3604574/b428529cbf79/kju-54-194-g002.jpg

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本文引用的文献

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Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing.采用焦磷酸测序法对前列腺癌中 28 个候选基因的 DNA 甲基化进行绝对定量分析。
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EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling.
EFEMP1 作为前列腺癌的新型 DNA 甲基化标志物:基于阵列的 DNA 甲基化和表达谱分析。
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DNA demethylase activity maintains intestinal cells in an undifferentiated state following loss of APC.DNA 去甲基化酶活性在 APC 缺失后维持肠道细胞处于未分化状态。
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