Zhu Meng, Zhang Ning, He Shuixiang
Department of Gastroenterology, First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, Shaanxi 710061, China.
Department of Pathology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.
Pathol Res Pract. 2014 Dec;210(12):909-15. doi: 10.1016/j.prp.2014.07.008. Epub 2014 Jul 30.
Evidence increasingly suggests that miR-106a is always elevated in gastric cancer; however, little is known about the expression trend and clinical significance in the whole process of gastric carcinogenesis and development. To investigate the dynamic changes of miR-106a in each stage during gastric carcinogenesis, we used formalin-fixed, paraffin-embedded (FFPE) tissues which had been reported to have valuable information for miRNA research in our previous studies. Here, we compared the expression of miR-106a in FFPE and fresh frozen tissues using real-time polymerase chain reaction. On the basis of the high correlation of miR-106a quantitative data from the two resources, FFPE samples were subsequently performed to elucidate the location and expression of miR-106a using in situ hybridization in sequential tissues, including normal gastric mucosa, chronic atrophic gastritis combined with various degrees of dysplasia, early and advanced gastric cancer. Finally, we found that miR-106a was similarly up-regulated in gastric cancer regardless of sample types although fragmentation existed inevitably in FFPE tissues. Notably, the frequency and extent of miR-106a expression gradually increased during the transition from atypical hyperplasia to advanced carcinoma and had already had positive signals in early precancerous lesions but negative signals in normal gastric mucosal epithelial cells. Our research, according to these results, indicated that FFPE samples can serve as an important research tool for miRNA field, and the early changes of miR-106a detected in such samples may have clinical application as a potential biomarker for the discovery and diagnosis of gastric cancer.
越来越多的证据表明,miR-106a在胃癌中总是呈升高状态;然而,对于其在胃癌发生发展全过程中的表达趋势及临床意义却知之甚少。为了研究miR-106a在胃癌发生各阶段的动态变化,我们使用了福尔马林固定、石蜡包埋(FFPE)组织,在我们之前的研究中已报道这些组织对于miRNA研究具有宝贵信息。在此,我们使用实时聚合酶链反应比较了FFPE组织和新鲜冷冻组织中miR-106a的表达。基于两种来源的miR-106a定量数据的高度相关性,随后对FFPE样本进行原位杂交,以阐明miR-106a在包括正常胃黏膜、伴有不同程度发育异常的慢性萎缩性胃炎、早期和进展期胃癌等连续组织中的定位和表达。最后,我们发现尽管FFPE组织中不可避免地存在片段化,但无论样本类型如何,miR-106a在胃癌中均同样上调。值得注意的是,miR-106a表达的频率和程度在从非典型增生向进展期癌转变的过程中逐渐增加,并且在早期癌前病变中已出现阳性信号,但在正常胃黏膜上皮细胞中为阴性信号。根据这些结果,我们的研究表明FFPE样本可作为miRNA领域的重要研究工具,在此类样本中检测到的miR-106a的早期变化可能作为发现和诊断胃癌的潜在生物标志物具有临床应用价值。