Xue Yue, Abou Tayoun Ahmad N, Abo Kristine M, Pipas J Marc, Gordon Stuart R, Gardner Timothy B, Barth Richard J, Suriawinata Arief A, Tsongalis Gregory J
Department of Pathology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Cancer Genet. 2013 Jun;206(6):217-21. doi: 10.1016/j.cancergen.2013.05.020. Epub 2013 Aug 9.
Since the discovery of small non-coding RNAs, the analysis of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. Evidence suggests that deregulated miRNA expression is associated with pancreatic cancer development. In this study, we analyzed the expression of several miRNAs in different types of pancreatic disease to determine if miRNA expression could aid in the diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its precursor, pancreatic intraepithelial neoplasm (PanIN). Pancreatic resection specimens were selected, which included PDAC (n = 16), benign pancreatic parenchyma from corresponding carcinoma cases (n = 16), chronic pancreatitis (n = 4), normal pancreatic parenchyma (n = 5), and PanIN (n = 5). The expression levels of five miRNA (miR-148a, miR-217, miR-21, miR-196a, and miR-10b) were assessed by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) assays. Our data demonstrate that compared to the normal pancreatic parenchyma, miR-148a and miR-217 expression levels were down-regulated in PanIN, particularly in PanIN II-III and PDAC, whereas the level of miR-196 was significantly up-regulated in PDAC and its precursor, PanIN II-III. In addition, we observed that miR-21 was significantly overexpressed in PDAC, and miR-10b was highly expressed in PanIN II-III. Our study demonstrates that certain miRNAs, especially miR-148a, miR-217, and miR-196a, are significantly deregulated in PDAC, including in the early stage of PDAC. These markers can potentially be used as diagnostic markers to distinguish PDAC and its precursor from benign lesions.
自从发现小型非编码RNA以来，对人类癌症中微小RNA（miRNA）表达模式的分析为癌症生物学提供了新的见解。有证据表明，miRNA表达失调与胰腺癌的发展有关。在本研究中，我们分析了几种miRNA在不同类型胰腺疾病中的表达，以确定miRNA表达是否有助于诊断胰腺导管腺癌（PDAC）及其前驱病变胰腺上皮内瘤变（PanIN）。选取了胰腺切除标本，包括PDAC（n = 16）、相应癌病例的良性胰腺实质（n = 16）、慢性胰腺炎（n = 4）、正常胰腺实质（n = 5）和PanIN（n = 5）。通过定量实时逆转录-聚合酶链反应（qRT-PCR）测定评估了五种miRNA（miR-148a、miR-217、miR-21、miR-196a和miR-10b）的表达水平。我们的数据表明，与正常胰腺实质相比，miR-148a和miR-217的表达水平在PanIN中下调，尤其是在PanIN II-III和PDAC中，而miR-196的水平在PDAC及其前驱病变PanIN II-III中显著上调。此外，我们观察到miR-21在PDAC中显著过表达，miR-10b在PanIN II-III中高表达。我们的研究表明，某些miRNA，尤其是miR-148a、miR-217和miR-196a，在PDAC中，包括在PDAC的早期阶段，有显著的失调。这些标志物有可能用作诊断标志物，以区分PDAC及其前驱病变与良性病变。
