Molecular subtypes of pancreatic cancer based on miRNA expression profiles have independent prognostic value
Molecular subtypes of pancreatic cancer based on miRNA expression profiles have independent prognostic value
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DOI：
10.1111/jgh.13253
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发表时间：
2016-06-01
影响因子：
4.1
通讯作者：
Jang, Jin-Young
中科院分区：
文献类型：
--
作者：
Namkung, Junghyun;Kwon, Wooil;Jang, Jin-Young
背景和目的：根据一些研究，改变的microRNA（miRNA）表达是许多癌症的典型特征，据报道与预后相关。虽然许多关于胰腺导管腺癌中miRNA的研究也试图确定预后生物标志物，但需要更多大规模的临床研究来确定结果的临床意义。本研究的目的是确定原发性胰腺肿瘤的凋亡相关分子亚型的miRNA表达profiling.Methods：通过使用芯片分析104名韩国胰腺肿瘤患者的1733个miRNA的表达谱。为了检测亚组信息预测患者的预后，我们采用无监督聚类方法，然后分析的关联的分子亚组与生存时间。然后，我们构建了一个分类器来预测亚组使用惩罚回归models.Results：我们已经确定了三个胰腺导管腺癌肿瘤亚型与预后的基础上的miRNA表达谱。这些亚型在相同临床条件下的生存时间有显著差异。这表明我们的预后分子亚组具有独立的预后效用。分子亚型可以用19种miRNA的分类器来预测。在19个特征性miRNA中，miR-106 b-star、miR-324- 3 p和miR-615与p53经典通路相关，miR-324、miR-145- 5 p、miR-26 b-5 p和miR-574- 3 p与考克斯-2中心通路相关。此外，我们构建了一个分类器，可用于确定新患者样本数据的分子亚组。需要进一步的研究进行验证。
Background and Aim:Altered microRNAs (miRNA) expression, a typical feature of many cancers, is reportedly associated with prognosis according to several studies. Although numerous studies on miRNAs in pancreatic ductal adenocarcinoma have also attempted to identify prognostic biomarkers, more large-scale clinical studies are needed to establish the clinical significance of the results. Present study aimed to identify prognosis-related molecular subtypes of primary pancreas tumors using miRNA expression profiling.Methods:Expression profiles of 1733 miRNAs were obtained by using microarray analysis of 104 pancreatic tumors of Korean patients. To detect subgroups informative in predicting the patient's prognosis, we applied unsupervised clustering methods and then analyzed the association of the molecular subgroups with survival time. Then, we constructed a classifier to predict the subgroup using penalized regression models.Results:We have determined three pancreatic ductal adenocarcinoma tumor subtypes associated with prognosis based on miRNA expression profiles. These subtypes showed significantly different survival time for patients with the same clinical conditions. This demonstrates that our prognostic molecular subgroup has independent prognostic utility. The molecular subtypes can be predicted with a classifier of 19 miRNAs. Of the 19 signature miRNAs, miR-106b-star, miR-324-3p, and miR-615 were related to a p53 canonical pathway, and miR-324, miR-145-5p, miR-26b-5p, and miR-574-3p were related to a Cox-2 centered pathway.Conclusions:Our prognostic molecular subtypes demonstrated that miRNA profiles could be used as prognostic markers. Additionally, we have constructed a classifier that may be used to determine the molecular subgroup of new patient sample data. Further studies are needed for validation.