Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients.
Aberrant promoter methylation of PPP1R3C and EFHD1 in plasma of colorectal cancer patients.
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DOI：
10.1002/cam4.273
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发表时间：
2014-10
期刊：
影响因子：
4
通讯作者：
Kaneda, Atsushi
中科院分区：
文献类型：
--
作者：
Takane, Kiyoko;Midorikawa, Yutaka;Yagi, Koichi;Sakai, Ayako;Aburatani, Hiroyuki;Takayama, Tadatoshi;Kaneda, Atsushi
DNA甲基化异常是结直肠癌中常见的表观遗传学改变。我们在前期的研究中，采用甲基化DNA免疫沉淀芯片技术结合5-氮-2 ′-脱氧胞苷处理后的基因再表达分析，对大肠癌基因组中广泛存在的甲基化基因进行了鉴定。在这些基因中，有12个基因在149例CRC样本中的异常甲基化率>75%，而在正常样本中没有。在这项研究中，我们的目标是找出任何这些甲基化基因用于CRC检测使用血浆DNA样本。甲基化特异性PCR和焦磷酸测序的引物被设计为12个基因中的7个。其中PPP 1 R3 C和EFHD 1在外周血细胞中很少发生高甲基化，但在24例CRC组织样本及其相应血浆样本中频繁发生高甲基化。在血浆样本中，PPP 1 R3 C在81%（97/120）的CRC患者中甲基化，但仅在19%（18/96）的非癌症患者中甲基化（P = 6 × 10−20，Fisher精确检验）。在与EFHD 1的联合分析中，53%（64/120）的CRC患者中这两个基因甲基化，但只有4%（4/96）的非癌症患者（P = 2 × 10−16），特异性高达96%。在90%（108/120）的CRC患者和36%（35/96）的对照患者中，两个基因中至少有一个甲基化，敏感性高达90%。与癌胚抗原的低敏感性相比（I期17%，II期40%）和CA 19 -9（I期为0%，II期为13%），对于早期CRC，异常甲基化的敏感性显著更高：PPP 1 R3 C甲基化在I期为92%（11/12），在II期为77%（23/30），至少一个基因的甲基化在I期为100%（12/12），在II期为87%（26/30）。PPP 1 R3 C甲基化或PPP 1 R3 C甲基化与EFHD 1甲基化联合应用在结直肠癌血浆标本中呈高度阳性，可能有助于结直肠癌的检测，尤其是早期结直肠癌。
Aberrant DNA methylation is a common epigenetic alteration involved in colorectal cancer (CRC). In our previous study, we performed methylated DNA immunoprecipitation-on-chip analysis combined with gene re-expression analysis by 5-aza-2′-deoxycytidine treatment, to identify methylation genes in CRC genome widely. Among these genes, 12 genes showed aberrant hypermethylation frequently in >75% of 149 CRC samples but did not in normal samples. In this study, we aim to find out any of these methylation genes to be utilized for CRC detection using plasma DNA samples. Primers for methylation-specific PCR and pyrosequencing were designed for seven of the 12 genes. Among them, PPP1R3C and EFHD1 were rarely hypermethylated in peripheral blood cells, but frequently hypermethylated in 24 CRC tissue samples and their corresponding plasma samples. In plasma samples, PPP1R3C was methylated in 81% (97/120) of CRC patients, but only in 19% (18/96) of noncancer patients (P = 6 × 10−20, Fisher's exact test). In combined analysis with EFHD1, both genes were methylated in 53% (64/120) of CRC patients, but only in 4% (4/96) of noncancer patients (P = 2 × 10−16), giving high specificity of 96%. At least one of the two genes was methylated in 90% (108/120) of CRC patients, and 36% (35/96) of control patients, giving high sensitivity of 90%. Compared with low sensitivity of carcinoembryonic antigen (17% at stage I, 40% at stage II) and CA19-9 (0% at stage I, 13% at stage II) for early-stage CRCs, sensitivity of aberrant methylation was significantly higher: PPP1R3C methylation at 92% (11/12) for stage I and 77% (23/30) for stage II, and methylation of at least one gene at 100% (12/12) for stage I and 87% (26/30) for stage II. PPP1R3C methylation or its combined use of EFHD1 methylation was highly positive in CRC plasma samples, and they might be useful in detection of CRC, especially for early-stage CRCs.
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影响因子：
168.9
作者：
Müller, HM;Oberwalder, M;Widschwendter, M
通讯作者：
Widschwendter, M
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
DOI：
10.1073/pnas.0704652104
发表时间：
2007-11-20
影响因子：
11.1
作者：
Shen, Lanlan;Toyota, Minoru;Issa, Jean-Pierre J.
通讯作者：
Issa, Jean-Pierre J.
影响因子：
7
作者：
Hinoue, Toshinori;Weisenberger, Daniel J.;Laird, Peter W.
通讯作者：
Laird, Peter W.
影响因子：
9.3
作者：
Lofton-Day, Catherine;Model, Fabian;Sledziewski, Andrew
通讯作者：
Sledziewski, Andrew