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通过综合分析鉴定胰腺癌中的新型治疗靶基因和通路

Identification of novel therapeutic target genes and pathway in pancreatic cancer by integrative analysis.

作者信息

Hu Bangli, Shi Cheng, Jiang Hai-Xing, Qin Shan-Yu

机构信息

Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.

出版信息

Medicine (Baltimore). 2017 Oct;96(42):e8261. doi: 10.1097/MD.0000000000008261.

DOI:10.1097/MD.0000000000008261
PMID:29049217
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5662383/
Abstract

BACKGROUND

Gene alterations are crucial to the molecular pathogenesis of pancreatic cancer. The present study was designed to identify the potential candidate genes in the pancreatic carcinogenesis.

METHODS

Gene Expression Omnibus database (GEO) datasets of pancreatic cancer tissue were retrieval and the differentially expressed genes (DEGs) from individual microarray data were merged. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction (PPI) networks, and gene coexpression analysis were performed.

RESULTS

Three GEO datasets, including 74 pancreatic cancer samples and 55 controls samples were selected. A total of 2325 DEGs were identified, including 1383 upregulated and 942 downregulated genes. The GO terms for molecular functions, biological processes, and cellular component were protein binding, small molecule metabolic process, and integral to membrane, respectively. The most significant pathway in KEGG analysis was metabolic pathways. PPI network analysis indicated that the significant hub genes including cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1), mitogen-activated protein kinase 3 (MAPK3), and phospholipase C, gamma 1 (PLCG1). Gene coexpression network analysis identified 4 major modules, and the potassium channel tetramerization domain containing 10 (KCTD10), kin of IRRE like (KIRREL), dipeptidyl-peptidase 10 (DPP10), and unc-80 homolog (UNC80) were the hub gene of each modules, respectively.

CONCLUSION

Our integrative analysis provides a comprehensive view of gene expression patterns associated with the pancreatic carcinogenesis.

摘要

背景

基因改变对胰腺癌的分子发病机制至关重要。本研究旨在识别胰腺癌发生过程中的潜在候选基因。

方法

检索胰腺癌组织的基因表达综合数据库(GEO)数据集,并合并来自各个微阵列数据的差异表达基因(DEG)。进行基因本体论(GO)富集分析、京都基因与基因组百科全书(KEGG)通路分析、蛋白质-蛋白质相互作用(PPI)网络分析和基因共表达分析。

结果

选择了三个GEO数据集,包括74个胰腺癌样本和55个对照样本。共鉴定出2325个DEG,其中1383个上调基因和942个下调基因。分子功能、生物学过程和细胞成分的GO术语分别为蛋白质结合、小分子代谢过程和膜整合。KEGG分析中最显著的通路是代谢通路。PPI网络分析表明,重要的枢纽基因包括细胞色素P450 2E1(CYP2E1)、丝裂原活化蛋白激酶3(MAPK3)和磷脂酶Cγ1(PLCG1)。基因共表达网络分析确定了4个主要模块,含钾通道四聚化结构域10(KCTD10)、IRRE样家族成员(KIRREL)、二肽基肽酶10(DPP10)和unc-80同源物(UNC80)分别是每个模块的枢纽基因。

结论

我们的综合分析提供了与胰腺癌发生相关的基因表达模式的全面视图。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9813/5662383/c0b8cffb3e32/medi-96-e8261-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9813/5662383/f48fa63d5bbc/medi-96-e8261-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9813/5662383/a725eadc18a3/medi-96-e8261-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9813/5662383/c0b8cffb3e32/medi-96-e8261-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9813/5662383/f48fa63d5bbc/medi-96-e8261-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9813/5662383/a725eadc18a3/medi-96-e8261-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9813/5662383/c0b8cffb3e32/medi-96-e8261-g006.jpg

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