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利用通路共表达分析鉴定甲状腺乳头状癌中的差异通路

Identification of differential pathways in papillary thyroid carcinoma utilizing pathway co-expression analysis.

作者信息

Qiu Wei-Hai, Chen Gui-Yan, Cui Lu, Zhang Ting-Ming, Wei Feng, Yang Yong

机构信息

Department of Endocrinology, Binzhou People's Hospital, Binzhou, 256600, Shandong Province, China.

出版信息

J BUON. 2016 Nov-Dec;21(6):1501-1509.

Abstract

PURPOSE

To identify differential pathways between papillary thyroid carcinoma (PTC) patients and normal controls utilizing a novel method which combined pathway with co-expression network.

METHODS

The proposed method included three steps. In the first step, we conducted pretreatments for background pathways and gained representative pathways in PTC. Subsequently, a co-expression network for representative pathways was constructed using empirical Bayes (EB) approach to assign a weight value for each pathway. Finally, random model was extracted to set the thresholds of identifying differential pathways.

RESULTS

We obtained 1267 representative pathways and their weight values based on the co-expressed pathway network, and then by meeting the criterion (Weight > 0.0296), 87 differential pathways in total across PTC patients and normal controls were identified. The top three ranked differential pathways were CREB phosphorylation, attachment of GPI anchor to urokinase plasminogen activator receptor (uPAR) and loss of function of SMAD2/3 in cancer.

CONCLUSIONS

In conclusion, we successfully identified differential pathways (such as CREB phosphorylation, attachment of GPI anchor to uPAR and post-translational modification: synthesis of GPI-anchored proteins) for PTC using the proposed pathway co-expression method, and these pathways might be potential biomarkers for target therapy and detection of PTC.

摘要

目的

利用一种将通路与共表达网络相结合的新方法,识别甲状腺乳头状癌(PTC)患者与正常对照之间的差异通路。

方法

所提出的方法包括三个步骤。第一步,我们对背景通路进行预处理,并在PTC中获得代表性通路。随后,使用经验贝叶斯(EB)方法构建代表性通路的共表达网络,为每个通路赋予一个权重值。最后,提取随机模型以设定识别差异通路的阈值。

结果

基于共表达通路网络,我们获得了1267条代表性通路及其权重值,然后通过满足标准(权重>0.0296),共识别出PTC患者和正常对照之间总共87条差异通路。排名前三的差异通路是CREB磷酸化、糖基磷脂酰肌醇(GPI)锚定到尿激酶型纤溶酶原激活剂受体(uPAR)以及癌症中SMAD2/3功能丧失。

结论

总之,我们使用所提出的通路共表达方法成功识别出PTC的差异通路(如CREB磷酸化、GPI锚定到uPAR以及翻译后修饰:GPI锚定蛋白的合成),这些通路可能是PTC靶向治疗和检测的潜在生物标志物。

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