Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cancer. 2013 Jun 1;119(11):1985-93. doi: 10.1002/cncr.28002. Epub 2013 Mar 1.
MicroRNAs (miRNAs) play critical roles in tumor development and progression. The finding that a single miRNA can regulate hundreds of genes places miRNAs at critical hubs of signaling pathways. For the current study, the authors investigated the miRNA expression profile of gastric adenocarcinomas and compared it with esophageal adenocarcinomas to better identify a unique miRNA signature of gastric adenocarcinoma.
miRNA expression profiles were obtained using 2 different proprietary microarray platforms on primary gastric adenocarcinoma tissue samples. The cross comparison of results identified 17 up-regulated miRNAs and 12 down-regulated miRNAs that overlapped in both platforms. Quantitative real-time polymerase chain reaction was performed for independent validation of a representative set of 8 miRNAs in gastric and esophageal adenocarcinomas compared with normal gastric mucosa or esophageal mucosa, respectively.
The deregulation of miR-146b-5p, miR-375, miR-148a, miR-31, and miR-451 was associated significantly with gastric adenocarcinomas. Conversely, deregulation of miR-21 (up-regulation) and miR-133b (down-regulation) was detectable in both gastric and esophageal adenocarcinomas. It was noteworthy that miR-200a was significantly down-regulated in gastric adenocarcinoma samples (P = .04) but was up-regulated in esophageal adenocarcinoma samples (P = .001). In addition, the expression level of miR-146b-5p displayed a strong correlation with the tumor stage of gastric cancer.
Gastric adenocarcinoma displayed a unique miRNA signature that distinguished it from esophageal adenocarcinoma. This specific signature may reflect differences in the etiology and/or molecular signaling in these 2 closely related cancers. The current findings suggest important miRNA candidates that can be investigated for their biological functions and for their possible diagnostic, prognostic, and therapeutic role in gastric adenocarcinoma.
微小 RNA（miRNA）在肿瘤的发生和发展中起着关键作用。单个 miRNA 可以调控数百个基因的发现，使 miRNA 处于信号通路的关键枢纽位置。在本研究中，作者研究了胃腺癌的 miRNA 表达谱，并与食管腺癌进行了比较，以更好地确定胃腺癌的独特 miRNA 特征。
使用两种不同的专有微阵列平台获得胃腺癌原发组织样本的 miRNA 表达谱。结果的交叉比较鉴定出在两个平台中均上调的 17 个 miRNA 和下调的 12 个 miRNA。进行定量实时聚合酶链反应（PCR），以独立验证在胃腺癌和食管腺癌中与正常胃黏膜或食管黏膜相比，代表性 miRNA 集合的 8 个 miRNA。
miR-146b-5p、miR-375、miR-148a、miR-31 和 miR-451 的失调与胃腺癌显著相关。相反，miR-21（上调）和 miR-133b（下调）的失调在胃腺癌和食管腺癌中均可检测到。值得注意的是，miR-200a 在胃腺癌样本中显著下调（P =.04），但在食管腺癌样本中上调（P =.001）。此外，miR-146b-5p 的表达水平与胃癌的肿瘤分期呈强相关。
胃腺癌显示出独特的 miRNA 特征，可将其与食管腺癌区分开来。这种特定的特征可能反映了这两种密切相关的癌症在病因和/或分子信号方面的差异。目前的研究结果表明，miRNA 是重要的候选物，可以研究其生物学功能及其在胃腺癌中的可能诊断、预后和治疗作用。
