MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma
MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma
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DOI：
10.1038/modpathol.2012.122
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发表时间：
2012-12-01
期刊：
影响因子：
7.5
通讯作者：
Johansen, Julia S.
中科院分区：
文献类型：
--
作者：
Schultz, Nicolai A.;Werner, Jens;Johansen, Julia S.
microRNA具有作为诊断癌症的生物标志物的潜力。本研究的目的是（1）在不使用显微解剖的情况下，确定来自胰腺导管腺癌、壶腹腺癌、正常胰腺和慢性胰腺炎的福尔马林固定石蜡包埋组织中的microRNA表达模式，以及（2）发现癌组织中新的诊断microRNA和microRNA组合。使用商业microRNA测定法分析了170例胰腺癌和107例壶腹腺癌组织中664种microRNA的表达。并与慢性胰腺炎、正常胰腺及十二指肠腺癌进行比较。总之，与正常胰腺相比，43种microRNA在胰腺癌中表达较高，41种microRNA表达降低。总之，与慢性胰腺炎相比，胰腺癌中有32种microRNA表达不同（17种高; 15种低）。这些microRNA中有几种以前与胰腺癌的诊断无关（例如，miR-492，miR-614，miR-622）。miR-614、miR-492、miR-622、miR-135 b * 和miR-196的表达差异最大。胰腺癌和壶腹腺癌的microRNA谱相关（0.990）。文献中描述的胰腺癌的microRNA表达谱与我们的发现一致，并且胰腺癌的microRNA谱（miR-196 b-miR-217）得到验证。我们发现了一个更显著的表达谱，miR-411和miR-198之间的差异（P = 2.06 x 10（-54））和使用19种microRNA的诊断性LASSO分类器（灵敏度98.5%;阳性预测值97.8%;准确度97.0%）。我们还确定了microRNA谱，以将壶腹腺癌细分为胰胆或肠型。总之，我们发现两种microRNA的组合可以大致区分肿瘤和非肿瘤样本。构建了一个诊断性的19 microRNA分类器，该分类器不需要显微切割就可以将胰腺癌和壶腹腺癌与慢性胰腺炎和正常胰腺区分开来，具有较高的灵敏度和准确性。正在进行的前瞻性研究将评估这些microRNA谱是否适用于细针活检，以早期诊断胰腺癌。Modern Pathology（2012）25，1609-1622; doi：10.1038/modpathol.2012.122; 2012年8月10日在线发表
MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b* and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P = 2.06 x 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from nonneoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer. Modern Pathology (2012) 25, 1609-1622; doi:10.1038/modpathol.2012.122; published online 10 August 2012