OBJECTIVES Barrett's esophagus (BE) is the precursor lesion and a major risk factor for esophageal adenocarcinoma (EAC). Although patients with BE undergo routine endoscopic surveillance, current screening methodologies have proven ineffective at identifying individuals at risk of EAC. Since microRNAs (miRNAs) have potential diagnostic and prognostic value as disease biomarkers, we sought to identify an miRNA signature of BE and EAC. METHODS High-throughput sequencing of miRNAs was performed on serum and tissue biopsies from 31 patients identified either as normal, gastroesophageal reflux disease (GERD), BE, BE with low-grade dysplasia (LGD), or EAC. Logistic regression modeling of miRNA profiles with Lasso regularization was used to identify discriminating miRNA. Quantitative reverse transcription polymerase chain reaction was used to validate changes in miRNA expression using 46 formalin-fixed, paraffin-embedded specimens obtained from normal, GERD, BE, BE with LGD or HGD, and EAC subjects. RESULTS A 3-class predictive model was able to classify tissue samples into normal, GERD/BE, or LGD/EAC classes with an accuracy of 80%. Sixteen miRNAs were identified that predicted 1 of the 3 classes. Our analysis confirmed previous reports indicating that miR-29c-3p and miR-193b-5p expressions are altered in BE and EAC and identified miR-4485-5p as a novel biomarker of esophageal dysplasia. Quantitative reverse transcription polymerase chain reaction validated 11 of 16 discriminating miRNAs. DISCUSSION Our data provide an miRNA signature of normal, precancerous, and cancerous tissue that may stratify patients at risk of progressing to EAC. We found that serum miRNAs have a limited ability to distinguish between disease states, thus limiting their potential utility in early disease detection.

中文翻译：

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巴雷特食管发病机制中的微 RNA 特征差异。

目的 巴雷特食管 (BE) 是食管腺癌 (EAC) 的前驱病变和主要危险因素。尽管 BE 患者接受了常规内窥镜监测，但目前的筛查方法已被证明在识别有 EAC 风险的个体方面无效。由于 microRNA (miRNA) 作为疾病生物标志物具有潜在的诊断和预后价值，因此我们试图鉴定 BE 和 EAC 的 miRNA 特征。方法 对 31 名正常、胃食管反流病 (GERD)、BE、低度不典型增生 (LGD) 的 BE 或 EAC 患者的血清和组织活检进行 miRNA 的高通量测序。使用 Lasso 正则化的 miRNA 配置文件的逻辑回归模型来识别有区别的 miRNA。使用从正常、GERD、BE、具有 LGD 或 HGD 的 BE 和 EAC 受试者获得的 46 个福尔马林固定、石蜡包埋的样本，使用定量逆转录聚合酶链反应来验证 miRNA 表达的变化。结果 3 类预测模型能够以 80% 的准确度将组织样本分类为正常、GERD/BE 或 LGD/EAC 类。鉴定出 16 个 miRNA，可预测 3 个类别中的 1 个。我们的分析证实了先前的报道，表明 miR-29c-3p 和 miR-193b-5p 在 BE 和 EAC 中的表达发生了改变，并将 miR-4485-5p 确定为食管发育不良的新生物标志物。定量逆转录聚合酶链反应验证了 16 种鉴别 miRNA 中的 11 种。讨论 我们的数据提供了正常、癌前病变、以及可能对有进展为 EAC 风险的患者进行分层的癌组织。我们发现血清 miRNA 区分疾病状态的能力有限，因此限制了它们在早期疾病检测中的潜在用途。