Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay.
Sensitive detection of colorectal cancer in peripheral blood by septin 9 DNA methylation assay.
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DOI：
10.1371/journal.pone.0003759
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Lofton-Day, Catherine
中科院分区：
文献类型：
--
作者：
Gruetzmann, Robert;Molnar, Bela;Pilarsky, Christian;Habermann, Jens K.;Schlag, Peter M.;Saeger, Hans D.;Miehlke, Stephan;Stolz, Thomas;Model, Fabian;Roblick, Uwe J.;Bruch, Hans-Peter;Koch, Rainer;Liebenberg, Volker;deVos, Theo;Song, Xiaoling;Day, Robert H.;Sledziewski, Andrew Z.;Lofton-Day, Catherine
结直肠癌（CRC）是癌症死亡的第二大原因，尽管在早期发现这种癌症的存活率超过90%。目前，在美国，只有不到45%的高危人群定期接受筛查，这表明需要更好的筛查测试。我们进行了两项病例对照研究，以验证一种基于血液的检测，该检测可识别CRC所有阶段血浆中的甲基化DNA。采用PCR方法分析血浆DNA中Septin 9 （SEPT9）的高甲基化，优化了354份样本（252份结直肠癌，102份对照）的临床表现，并在309份样本（126份结直肠癌，183份对照）的盲法独立研究中进行了验证。168例息肉和411例其他疾病对照也进行了评估。在训练研究的基础上，基于sept9的分类检测出120/252例crc（48%）和7/102例对照（7%）。在试验研究中，73/126个crc（58%）和18/183个对照样本（10%）的SEPT9阳性验证了训练集的结果。纳入一个额外的测量重复可将该方法在测试集中的灵敏度提高到72%（检测到90/125个crc），同时保持90%的特异性（对照组为19/183）。其他癌症（11/96）和非癌症（41/315）的血浆阳性率较低。息肉检出率（bbb1cm）为~ 20%。血浆中SEPT9 DNA甲基化分析代表了一种直接、微创的方法来检测所有阶段的CRC，有可能满足筛查人群中未满足的增加依从性的需求。进一步的临床试验是必要的。
Colorectal cancer (CRC) is the second leading cause of cancer deaths despite the fact that detection of this cancer in early stages results in over 90% survival rate. Currently less than 45% of at-risk individuals in the US are screened regularly, exposing a need for better screening tests. We performed two case-control studies to validate a blood-based test that identifies methylated DNA in plasma from all stages of CRC. Using a PCR assay for analysis of Septin 9 (SEPT9) hypermethylation in DNA extracted from plasma, clinical performance was optimized on 354 samples (252 CRC, 102 controls) and validated in a blinded, independent study of 309 samples (126 CRC, 183 controls). 168 polyps and 411 additional disease controls were also evaluated. Based on the training study SEPT9-based classification detected 120/252 CRCs (48%) and 7/102 controls (7%). In the test study 73/126 CRCs (58%) and 18/183 control samples (10%) were positive for SEPT9 validating the training set results. Inclusion of an additional measurement replicate increased the sensitivity of the assay in the testing set to 72% (90/125 CRCs detected) while maintaining 90% specificity (19/183 for controls). Positive rates for plasmas from the other cancers (11/96) and non-cancerous conditions (41/315) were low. The rate of polyp detection (>1 cm) was ∼20%. Analysis of SEPT9 DNA methylation in plasma represents a straightforward, minimally invasive method to detect all stages of CRC with potential to satisfy unmet needs for increased compliance in the screening population. Further clinical testing is warranted.
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