Circulating nucleosomes as new blood-based biomarkers for detection of colorectal cancer.
Circulating nucleosomes as new blood-based biomarkers for detection of colorectal cancer.
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DOI：
10.1186/s13148-017-0351-5
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发表时间：
2017
影响因子：
5.7
通讯作者：
D'Hondt L
中科院分区：
文献类型：
--
作者：
Rahier JF;Druez A;Faugeras L;Martinet JP;Géhénot M;Josseaux E;Herzog M;Micallef J;George F;Delos M;De Ronde T;Badaoui A;D'Hondt L
结肠镜检查目前被广泛接受为检测结直肠癌（CRC）的金标准，在手术过程中可检测高达95%的癌前病变。然而，大多数国家存在某些限制，包括费用和获得程序。此外，结肠镜检查是一种侵入性技术，具有内窥镜手术固有的风险。因此，替代筛查测试，特别是粪便潜血测试，已被广泛用于前缐筛查。由于对结肠镜检查和粪便筛查方法的依从性有限，促使人们研究基于血液的检测，作为识别有风险的个体的替代方法，然后将其转诊接受结肠镜检查。血液中核小体总水平的增加与肿瘤负荷和恶性进展相关。在这里，我们报告的第一次，循环无细胞核小体（cf-核小体）的CRC相关的表观遗传配置文件。12表观遗传cf-核小体表位的水平进行了测量，在58个人的血清中提到的大肠癌内镜筛查。多变量分析定义了一组年龄调整的四个cf-核小体，其提供了0.97的AUC，用于区分CRC与健康对照，在早期具有高灵敏度（I期和II期的灵敏度分别为75和86，特异性为90%）。四种cf-核小体生物标志物的第二种组合提供了0.72的AUC，用于区分息肉与健康组。这项研究表明，通过简单的ELISA分析血清样本中不同的cf-核小体结构的组合是一种有前途的方法，以确定患者的CRC风险。本文的在线版本（doi：10.1186/s13148-017-0351-5）包含补充材料，可供授权用户使用。
Colonoscopy is currently widely accepted as the gold standard for detection of colorectal cancer (CRC) providing detection of up to 95% of pre-cancerous lesions during the procedure. However, certain limitations exist in most countries including cost and access to the procedure. Moreover, colonoscopy is an invasive technique with risk inherent to the endoscopic procedure. For this reason, alternative screening tests, in particular, fecal occult blood-based tests, have been widely adopted for frontline screening. Limited compliance to colonoscopy and fecal screening approaches has prompted research on blood-based tests as an alternative approach to identifying individuals at risk who could then be referred for colonoscopy. Increased total levels of nucleosomes in the blood have been associated with tumor burden and malignancy progression. Here, we report for the first time, CRC-associated epigenetic profiles of circulating cell-free nucleosomes (cf-nucleosomes). Levels of 12 epigenetic cf-nucleosome epitopes were measured in the sera of 58 individuals referred for endoscopic screening for CRC. Multivariate analysis defined an age-adjusted panel of four cf-nucleosomes that provided an AUC of 0.97 for the discrimination of CRC from healthy controls with high sensitivity at early stages (sensitivity of 75 and 86 at 90% specificity for stages I and II, respectively). A second combination of four cf-nucleosome biomarkers provided an AUC of 0.72 for the discrimination of polyps from the healthy group. This study suggests that a combination of different cf-nucleosome structures analyzed in serum samples by a simple ELISA is a promising approach to identify patients at risk of CRC. The online version of this article (doi:10.1186/s13148-017-0351-5) contains supplementary material, which is available to authorized users.