Identification of the Key Genes and Pathways in Esophageal Carcinoma

Gastroenterology Research and Practice, Oct 2016

Objective. Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods. 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results. A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion. The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

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Identification of the Key Genes and Pathways in Esophageal Carcinoma

Identification of the Key Genes and Pathways in Esophageal Carcinoma Peng Su, Shiwang Wen, Yuefeng Zhang, Yong Li, Yanzhao Xu, Yonggang Zhu, Huilai Lv, Fan Zhang, Mingbo Wang, and Ziqiang Tian Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China Received 28 March 2016; Revised 1 July 2016; Accepted 11 July 2016 Academic Editor: Robert Odze Copyright © 2016 Peng Su et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Objective. Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods. 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results. A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion. The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis. 1. Introduction Esophageal carcinoma (EC) is the sixth leading cause of cancer mortality in males and the ninth leading cause of cancer mortality in females in 2012 worldwide [1]. The highest incident rates of EC are found in Eastern Asia, Southern Africa, and Eastern Africa and the lowest incidence rate of EC is found in Western Africa [1]. Esophageal carcinoma is usually 3 to 4 times more common among men than women. The 5-year overall survival ranges from 15% to 25% [2]. In China, it is predicted that EC is the fourth leading cause of cancer deaths in males and females after lung and bronchus, stomach, and liver in 2015 [3]. EC is classified as esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) according to histological type and ESCC is the predominant histological type of EC in the world [2]. It is reported that tobacco consumption, alcohol consumption, and low intake of fruits and vegetables are major risk factors for ESCC [4]. Overweight, obesity, gastroesophagus reflux disease (GERD), and Barrett’s esophagus increase incidence risk of EAC [1, 5]. In addition to the above-mentioned environmental factors, abnormal expression of miRNA and genes and methylation of genes and SNPs are associated with EC tumorigenesis and development. miR-219-1 rs107822G > A polymorphism might significantly decrease ESCC risk through changing individual susceptibility to Chinese Kazakhs [5]. The cases carrying the GG variant homozygote have a significant 2.81-fold increased risk of EC [6]. miR-330-3p promotes cell growth, cell migration, and invasion and inhibits cisplatin-induced apoptosis in ESCC cells via suppression of PDCD4 expression [7]. miR-199a-5p downregulation contributes to enhancing EC cell proliferation through upregulation of mitogen-activated protein kinase kinase kinase-11 [8]. DACT2 is frequently methylated in human esophageal cancer; methylated DATC2 accelerates esophageal cancer development by activating Wnt signaling [9]. RUNX3 methylation is associated with an increased risk, progression, and poor survival in EC [10]. Currently, the molecular mechanism of EC was unclear. In this study, we used bioinformatics methods to analyze the mRNA expression data of EC, which were available on the GEO database, to identify key genes and pathways in EC, aiming to provide valuable information for further pathogenesis mechanism elucidation and provide ground work for therapeutic targets identification for EC. 2. Materials and Methods2.1. Expression Profile Microarray Gene expression profiles data were downloaded from the Gene Expression Omnibus (GEO) data repository (http://www.ncbi.nlm.nih.gov/geo/). The datasets of patients receiving preoperative treatment before oesophagectomy and cell lines receiving drug stimulus were excluded. Total of 5 mRNA expression datasets of EC tissues/cell lines comprising GSE53625, GSE33810, GSE17351, GSE9982, and GSE12737 were included in our study. 2.2. Identification of DEGs The raw d (...truncated)


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Peng Su, Shiwang Wen, Yuefeng Zhang, Yong Li, Yanzhao Xu, Yonggang Zhu, Huilai Lv, Fan Zhang, Mingbo Wang, Ziqiang Tian. Identification of the Key Genes and Pathways in Esophageal Carcinoma, Gastroenterology Research and Practice, 2016, 2016, DOI: 10.1155/2016/2968106