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基于生物信息学分析预测甲状腺乳头状癌中的关键基因和信号通路。

Key genes and pathways predicted in papillary thyroid carcinoma based on bioinformatics analysis.

作者信息

Yu J, Mai W, Cui Y, Kong L

机构信息

Department of Head and Neck Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150081, China.

Department of Orthopedics, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150081, China.

出版信息

J Endocrinol Invest. 2016 Nov;39(11):1285-1293. doi: 10.1007/s40618-016-0491-z. Epub 2016 Jun 1.

Abstract

PURPOSE

The aim of this study was to predict the key genes and pathways associated with papillary thyroid carcinoma (PTC).

METHODS

Based on the microarray data of GSE3467 from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between 9 PTC samples and 9 normal controls. With the identified DEGs, functional enrichment analyses were performed. Additionally, a protein-protein interaction network was constructed to screened out some key gene nodes. These key nodes were then performed clustering analysis and pathway enrichment analysis. Furthermore, human PTC-associated network was constructed based on these key genes to investigate the potential relationships between genes and PTC.

RESULTS

A total of 651 up-regulated and 692 down-regulated DEGs were identified in PTC samples compared with controls. The up-regulated DEGs, such as complement component 3 (C3), were mainly enriched in hsa04610:Complement and coagulation cascades. The down-regulated DEGs, including paired box 8 (PAX8), peroxisome proliferator-activated receptor gamma (PPARG), and cadherin 1, type 1 were found enriched in hsa05216:Thyroid cancer. Total 33 DEGs were considered as key genes, such as PAX8, PPARG and Jun proto-oncogene (JUN). Disease-associated network analysis found that 15 key genes such as JUN, PPARG and matrix metallopeptidase 9 (MMP9) were involved in this network.

CONCLUSIONS

DEGs of C3, PPARG, PAX8, JUN and MMP9 were differentially expressed in PTC samples and may be used as potential biomarkers in the diagnosis and treatment of PTC. Additionally, pathways of complement and coagulation cascades and thyroid cancer may also play important roles in the development of PTC.

摘要

目的

本研究旨在预测与甲状腺乳头状癌(PTC)相关的关键基因和通路。

方法

基于基因表达综合数据库中GSE3467的微阵列数据,我们鉴定了9个PTC样本和9个正常对照之间的差异表达基因(DEG)。利用鉴定出的DEG进行功能富集分析。此外,构建蛋白质-蛋白质相互作用网络以筛选出一些关键基因节点。然后对这些关键节点进行聚类分析和通路富集分析。此外,基于这些关键基因构建人PTC相关网络,以研究基因与PTC之间的潜在关系。

结果

与对照相比,在PTC样本中总共鉴定出651个上调和692个下调的DEG。上调的DEG,如补体成分3(C3),主要富集于hsa04610:补体和凝血级联反应。下调的DEG,包括配对盒8(PAX8)、过氧化物酶体增殖物激活受体γ(PPARG)和钙黏蛋白1,1型,发现富集于hsa05216:甲状腺癌。总共33个DEG被认为是关键基因,如PAX8、PPARG和原癌基因Jun(JUN)。疾病相关网络分析发现,15个关键基因,如JUN、PPARG和基质金属蛋白酶9(MMP9)参与了该网络。

结论

C3、PPARG、PAX8、JUN和MMP9的DEG在PTC样本中差异表达,可能作为PTC诊断和治疗的潜在生物标志物。此外,补体和凝血级联反应以及甲状腺癌通路在PTC的发生发展中也可能起重要作用。

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