Diagnostic Potential of Cell-Free and Exosomal MicroRNAs in the Identification of Patients with High-Risk Colorectal Adenomas.

Diagnostic Potential of Cell-Free and Exosomal MicroRNAs in the Identification of Patients with High-Risk Colorectal Adenomas.
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DOI:
10.1371/journal.pone.0160722
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Kusunoki M
Kusunoki M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Uratani R;Toiyama Y;Kitajima T;Kawamura M;Hiro J;Kobayashi M;Tanaka K;Inoue Y;Mohri Y;Mori T;Kato T;Goel A;Kusunoki M

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尽管人们越来越关注开发循环microRNA(miRNA)作为用于检测高危结直肠腺瘤和早期CRC的非侵入性诊断生物标志物,但血清与外泌体miRNA的比较诊断意义仍未探索。基于已发表的文献,我们通过研究20例正常结肠粘膜、27例腺瘤和19例CRC组织中miRNA组的表达进行了初步发现。我们通过定量26名腺瘤患者和47名健康对照的总血清和外泌体中候选miRNA的表达进行了后续验证,并评估了其在结直肠腺瘤中的临床意义和潜在诊断价值。我们观察到四种miRNA,miR-21,miR-29 a,miR-92 a和miR-135 b,在结直肠腺瘤中的表达显著高于正常结肠粘膜。在验证过程中,血清中miR-21、miR-29 a和miR-92 a的表达在腺瘤中显著高于健康对照,与结肠直肠内腺瘤大小和腺瘤总数显著相关,并显著区分晚期腺瘤患者。相比之下,尽管腺瘤患者中的外泌体miR-21和miR-29 a水平显著高于健康志愿者,但只有外泌体miR-21与腺瘤大小和腺瘤总数显著相关,并且可以区分高危腺瘤患者。与外来体miRNA相比,血清中miR-21、miR-29 a和miR-92 a水平是高危腺瘤性息肉患者的上级诊断生物标志物。
Although there is a growing interest in developing circulating microRNA (miRNA) as noninvasive diagnostic biomarkers for the detection of high-risk colorectal adenomas and early-stage CRCs, but the comparative diagnostic significance of serum vs. exosomal miRNAs remains unexplored. Based upon published literature, we performed an initial discovery step by investigating the expression of a miRNA panel in 20 normal colonic mucosa, 27 adenomas, and 19 CRC tissues. We performed subsequent validation by quantifying expression of candidate miRNAs in total serum and in exosomes from 26 adenoma patients and 47 healthy controls, and evaluated their clinical significance and potential diagnostic value in colorectal adenomas. We observed that the expression of four miRNAs, miR-21, miR-29a, miR-92a, and miR-135b, was significantly higher in colorectal adenomas vs. normal colonic mucosa. During validation, expression of miR-21, miR-29a and miR-92a in serum was significantly higher in adenomas vs. healthy controls, significantly correlated with adenoma size and total adenoma number within the colorectum, and significantly discriminated patients with advanced adenomas. In contrast, although exosomal miR-21 and miR-29a levels in adenoma patients were significantly higher than those of healthy volunteers, only exosomal miR-21 significantly correlated with adenoma size and total adenoma number, and could discriminate patients with high-risk adenomas. Compared to exosomal miRNAs, serum levels of miR-21, miR-29a and miR-92a are superior diagnostic biomarkers in patients with high-risk adenomatous polyps.
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