Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer.
Genome-scale discovery of DNA-methylation biomarkers for blood-based detection of colorectal cancer.
复制标题
DOI：
10.1371/journal.pone.0050266
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Laird PW
中科院分区：
文献类型：
--
作者：
Lange CP;Campan M;Hinoue T;Schmitz RF;van der Meulen-de Jong AE;Slingerland H;Kok PJ;van Dijk CM;Weisenberger DJ;Shen H;Tollenaar RA;Laird PW
对于用于早期非侵入性结直肠癌检测的准确生物标志物的需求日益增加。我们采用了一种基因组规模的标记物发现方法，以确定和验证候选DNA甲基化生物标志物的血液为基础的检测结直肠癌。我们使用了来自711个结直肠肿瘤，53个匹配的邻近正常结肠组织样本，286个健康血液样本和15种不同癌症类型的4，201个肿瘤样本的DNA甲基化数据。DNA甲基化数据由Illumina Infinium HumanMethylation 27和HumanMethylation 450平台生成，其分别确定27，578和482，421个CpG位点的甲基化状态。我们首先进行了多步标记物选择，以确定在所有结直肠肿瘤中具有高甲基化的候选标记物，同时在健康样本和其他癌症类型中具有低甲基化。然后，我们使用来自107名结直肠癌患者和98名非结直肠癌对照的治疗前血浆和血清样本，通过结肠镜检查确认，以验证候选标记物。我们选择了两个标记物用于进一步评估：甲基化THBD（THBD-M）和甲基化C9 orf 50（C9 orf 50-M）。当对临床血浆和血清样品进行测试时，这些标志物优于癌胚抗原（CEA）血清测量，并导致早期结直肠癌检测的高灵敏度和特异性测试性能。我们对基于血液的DNA甲基化标志物的系统性标志物发现和验证研究产生了两种新的结直肠癌生物标志物THBD-M和C9 orf 50-M。特别是THBD-M在临床样品中表现出良好的性能，证明了其进一步优化和临床测试的合理性。
There is an increasing demand for accurate biomarkers for early non-invasive colorectal cancer detection. We employed a genome-scale marker discovery method to identify and verify candidate DNA methylation biomarkers for blood-based detection of colorectal cancer. We used DNA methylation data from 711 colorectal tumors, 53 matched adjacent-normal colonic tissue samples, 286 healthy blood samples and 4,201 tumor samples of 15 different cancer types. DNA methylation data were generated by the Illumina Infinium HumanMethylation27 and the HumanMethylation450 platforms, which determine the methylation status of 27,578 and 482,421 CpG sites respectively. We first performed a multistep marker selection to identify candidate markers with high methylation across all colorectal tumors while harboring low methylation in healthy samples and other cancer types. We then used pre-therapeutic plasma and serum samples from 107 colorectal cancer patients and 98 controls without colorectal cancer, confirmed by colonoscopy, to verify candidate markers. We selected two markers for further evaluation: methylated THBD (THBD-M) and methylated C9orf50 (C9orf50-M). When tested on clinical plasma and serum samples these markers outperformed carcinoembryonic antigen (CEA) serum measurement and resulted in a high sensitive and specific test performance for early colorectal cancer detection. Our systematic marker discovery and verification study for blood-based DNA methylation markers resulted in two novel colorectal cancer biomarkers, THBD-M and C9orf50-M. THBD-M in particular showed promising performance in clinical samples, justifying its further optimization and clinical testing.
登录
查看更多内容
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
影响因子：
3.7
作者：
Campan M;Moffitt M;Houshdaran S;Shen H;Widschwendter M;Daxenbichler G;Long T;Marth C;Laird-Offringa IA;Press MF;Dubeau L;Siegmund KD;Wu AH;Groshen S;Chandavarkar U;Roman LD;Berchuck A;Pearce CL;Laird PW
通讯作者：
Laird PW
影响因子：
3.9
作者：
Carvalho RH;Haberle V;Hou J;van Gent T;Thongjuea S;van Ijcken W;Kockx C;Brouwer R;Rijkers E;Sieuwerts A;Foekens J;van Vroonhoven M;Aerts J;Grosveld F;Lenhard B;Philipsen S
通讯作者：
Philipsen S
影响因子：
9.8
作者：
Leung, WK;To, KF;Sung, JJY
通讯作者：
Sung, JJY