Feasibility of MicroRNAs as Biomarkers for Barrett's Esophagus Progression: A Pilot Cross-Sectional, Phase 2 Biomarker Study
Feasibility of MicroRNAs as Biomarkers for Barrett's Esophagus Progression: A Pilot Cross-Sectional, Phase 2 Biomarker Study
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DOI：
10.1038/ajg.2011.37
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发表时间：
2011-06-01
影响因子：
9.8
通讯作者：
Christenson, L. K.
中科院分区：
文献类型：
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作者：
Bansal, Ajay;Lee, I. H.;Christenson, L. K.
结论：使用生物标志物对Barrett食管（BE）进行风险分层仍然是一个重要的目标。我们评估了新的microRNA（miRNA）生物标志物用于预测BE dysplasia. METHODS的可行性和临床准确性：来自前瞻性组织库的成对新鲜冷冻和苏木精/伊红标本，其中仅活检有兴趣的病变（即，肠上皮化生（IM）或高度异型增生（HGD）/食管腺癌（EAC））占据活检区域的> 50%。通过微阵列测定组织miRNA表达，并通过定量逆转录-PCR（qRT-PCR）验证。三组进行了比较，A组，IM组织从BE患者无异型增生;组B，IM组织从C组患者;和C组，异型增生组织从BE患者HGD/EAC。结果：总体而言，22例BE患者，11例有和无异型增生（平均年龄分别为64 +/-8.2和63 +/-11.6岁，所有白人男性）进行了评价。通过高通量分析鉴定了9种miRNA（miR-15 b、-21、-192、-205、486 - 5p、-584、-1246、let-7a和-7d），qRT-PCR证实了miR-15 b、-21、486 - 5p和let-7a的表达。先前在BE患者中描述的4种miRNAs中的两种（miR-145和-203，而不是-196a和-375）也表现出差异表达。miRNA对HGD/EAC的敏感性和特异性分别为miR-15 b：87和80%，miR-21：93和70%，miR-203：87和90%，miR-486 - 5p：82和55%，miR-let-7a：88和70%。miRNA-15b、-21和-203表现出场效应（即，A组和B组组织，虽然组织学上相似，但表现出不同的miRNA表达）。结论：该初步研究证明了miRNA以合理的临床准确性区分有和无异型增生的BE患者的可行性。然而，具体的miRNAs需要在未来的前瞻性试验中进一步评估。
OBJECTIVES: Risk stratification of Barrett's esophagus (BE) using biomarkers remains an important goal. We evaluated feasibility and clinical accuracy of novel microRNA (miRNA) biomarkers for prediction of BE dysplasia.METHODS: Paired fresh-frozen and hematoxylin/eosin specimens from a prospective tissue repository where only biopsies with the lesion of interest (i.e., intestinal metaplasia (IM) or high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC)) occupying >50% of biopsy area were included. Tissue miRNA expression was determined by microarrays and validated by quantitative reverse transcription-PCR (qRT-PCR). Three groups were compared-group A, IM tissues from BE patients without dysplasia; group B, IM tissues from group C patients; and group C, dysplastic tissues from BE patients with HGD/EAC.RESULTS: Overall, 22 BE patients, 11 with and without dysplasia (mean age 64 +/- 8.2 and 63 +/- 11.6 years, respectively, all Caucasian males) were evaluated. Nine miRNAs were identified by high-throughout analysis (miR-15b, -21, -192, -205, 486-5p, -584, -1246, let-7a, and -7d) and qRT-PCR confirmed expression of miR-15b, -21, 486-5p, and let-7a. Two of 4 miRNAs (miR-145 and -203, but not -196a and -375) previously described in BE patients also exhibited differential expression. Sensitivity and specificity of miRNAs for HGD/EAC were miR-15b: 87 and 80%, miR-21: 93 and 70%, miR-203: 87 and 90%, miR-486-5p: 82 and 55%, and miR-let-7a: 88 and 70%. MiRNA-15b, -21, and -203 exhibited field effects (i.e., groups A and B tissues while histologically similar yet exhibited different miRNA expression).CONCLUSIONS: This pilot study demonstrates feasibility of miRNAs to discriminate BE patients with and without dysplasia with reasonable clinical accuracy. However, the specific miRNAs need to be evaluated further in future prospective trials.