Division of Gastroenterology, Department of Medicine, Duke University, DUMC 3913, Durham, NC, 27710, USA,
Dig Dis Sci. 2013 Nov;58(11):3178-88. doi: 10.1007/s10620-013-2806-7. Epub 2013 Aug 8.
Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neoplasia are needed.
We sought to assess whether differential expression of microRNAs could discriminate between squamous epithelium, Barrett's esophagus (BE), and EAC.
We analyzed microRNA expression in a discovery cohort of human endoscopic biopsy samples from 36 patients representing normal squamous esophagus (n = 11), BE (n = 14), and high-grade dysplasia/EAC (n = 11). RNA was assessed using microarrays representing 847 human microRNAs followed by quantitative real-time polymerase chain reaction (qRT-PCR) verification of nine microRNAs. In a second cohort (n = 18), qRT-PCR validation of five miRNAs was performed. Expression of 59 microRNAs associated with BE/EAC in the literature was assessed in our training cohort. Known esophageal cell lines were used to compare miRNA expression to tissue miRNAs.
After controlling for multiple comparisons, we found 34 miRNAs differentially expressed between squamous esophagus and BE/EAC by microarray analysis. However, miRNA expression did not reliably differentiate non-dysplastic BE from EAC. In the validation cohort, all five microRNAs selected for qRT-PCR validation differentiated between squamous samples and BE/EAC. Microarray results supported 14 of the previously reported microRNAs associated with BE/EAC in the literature. Cell lines did not generally reflect miRNA expression found in vivo.
These data indicate that miRNAs differ between squamous esophageal epithelium and BE/EAC, but do not distinguish between BE and EAC. We suggest prospective evaluation of miRNAs in patients at high risk for EAC.
目前的策略未能在疾病发展到晚期和无法治愈之前发现大多数食管腺癌（EAC）患者。鉴于 EAC 预后不佳，需要提高早期食管肿瘤的检测能力。
我们旨在评估 microRNA 的差异表达是否可以区分鳞状上皮、巴雷特食管（BE）和 EAC。
我们分析了 36 名患者的内镜活检样本中的 microRNA 表达，这些患者代表正常的鳞状食管（n = 11）、BE（n = 14）和高级别异型增生/EAC（n = 11）。使用代表 847 种人类 microRNA 的微阵列进行 RNA 分析，随后通过定量实时聚合酶链反应（qRT-PCR）验证了 9 种 microRNA。在第二个队列（n = 18）中，对五种 miRNA 进行了 qRT-PCR 验证。在我们的训练队列中评估了与 BE/EAC 相关的 59 种文献中已知的 microRNAs 的表达。使用已知的食管细胞系将 microRNA 表达与组织 microRNA 进行比较。
在控制了多次比较后，我们通过微阵列分析发现 34 种 microRNA 在鳞状食管和 BE/EAC 之间差异表达。然而，miRNA 表达并不能可靠地区分非异型增生性 BE 与 EAC。在验证队列中，选择用于 qRT-PCR 验证的五种 microRNA 均能区分鳞状样本和 BE/EAC。微阵列结果支持文献中与 BE/EAC 相关的 14 种先前报道的 microRNA。细胞系通常不能反映体内发现的 microRNA 表达。
这些数据表明，miRNA 在鳞状食管上皮和 BE/EAC 之间存在差异，但不能区分 BE 和 EAC。我们建议在 EAC 高危患者中前瞻性评估 microRNA。
