Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer.

Plasma miR-601 and miR-760 are novel biomarkers for the early detection of colorectal cancer.
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血浆 miR-601 和 miR-760 是早期检测结直肠癌的新型生物标志物

DOI:
10.1371/journal.pone.0044398
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Du X
Du X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang Q;Huang Z;Ni S;Xiao X;Xu Q;Wang L;Huang D;Tan C;Sheng W;Du X

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背景结直肠癌(CRC)是世界范围内的主要死亡原因。迫切需要灵敏、非侵入性的诊断筛查方法来提高其存活率。稳定的循环microRNA为包括癌症在内的多种疾病的早期诊断提供了独特的机会。我们的目标是找到新的血浆miRNAs,可用作检测CRC的生物标志物。方法学/主要发现根据对来自10名CRC患者或10名健康对照的合并血浆样品进行的miRNA谱分析的结果,一组miRNA(hsa-miR-10a、-19a、-22*、-24、-92a、125a-5p、-141、-150、-188-3p、-192、-210、-221、-224*、-376a、-425*、-495、-572、-601、-720、-760和hsa-let-7a,-7e)在CRC血浆中失调,倍数变化>5。在对另外191名独立个体(90名CRC、43名晚期腺瘤和58名健康参与者)进行qRT-PCR大规模验证后,我们发现与健康对照相比,结肠直肠瘤形成(癌和晚期腺瘤)中血浆miR-601和miR-760的水平显著降低。ROC曲线分析显示,血浆miR-601和miR-760对晚期肿瘤具有显著的诊断价值。这两种miRNA一起产生用于将CRC与正常对照分开的具有83.3%灵敏度和69.1%特异性的0.792的AUC,并且产生用于将晚期腺瘤与正常对照区分开的具有72.1%灵敏度和62.1%特异性的0.683的AUC。结论/意义血浆miR-601和miR-760可能作为有前途的非侵入性生物标志物用于早期检测CRC。
Background Colorectal cancer (CRC) is a major cause of death worldwide. Sensitive, non-invasive diagnostic screen methods are urgently needed to improve its survival rates. Stable circulating microRNA offers unique opportunities for the early diagnosis of several diseases, including cancers. Our aim has been to find new plasma miRNAs that can be used as biomarkers for the detection of CRC. Methodology/Principal Findings According to the results of miRNA profiling performed on pooling plasma samples form 10 CRC patients or 10 healthy controls, a panel of miRNAs (hsa-miR-10a, -19a, -22*, -24, -92a, 125a-5p, -141, -150, -188-3p, -192, -210, -221, -224*, -376a, -425*, -495, -572, -601, -720, -760 and hsa-let-7a, -7e) were deregulated in CRC plasma with fold changes >5. After large scale validation by qRT-PCR performed on another 191 independent individuals (90 CRC, 43 advanced adenoma and 58 healthy participants), we found that the levels of plasma miR-601 and miR-760 were significantly decreased in colorectal neoplasia (carcinomas and advanced adenomas) compared with healthy controls. ROC curve analysis showed that plasma miR-601 and miR-760 were of significant diagnostic value for advanced neoplasia. These two miRNAs together yield an AUC of 0.792 with 83.3% sensitivity and 69.1% specificity for separating CRC from normal controls, and yield an AUC of 0.683 with 72.1% sensitivity and 62.1% specificity in discriminating advanced adenomas from normal controls. Conclusions/Significance Plasma miR-601 and miR-760 can potentially serve as promising non-invasive biomarkers for the early detection of CRC.
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