Oncotarget

Research Papers:

Identification of molecular targets for esophageal carcinoma diagnosis using miRNA-seq and RNA-seq data from The Cancer Genome Atlas: a study of 187 cases

Jiang-Hui Zeng, Dan-Dan Xiong, Yu-Yan Pang, Yu Zhang, Rui-Xue Tang, Dian-Zhong Luo and Gang Chen _

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Oncotarget. 2017; 8:35681-35699. https://doi.org/10.18632/oncotarget.16051

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Abstract

Jiang-hui Zeng1,*, Dan-dan Xiong1,*, Yu-yan Pang1, Yu Zhang1, Rui-xue Tang1, Dian-zhong Luo1, Gang Chen1

1Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, China

*These authors contributed equally to this work

Correspondence to:

Gang Chen, email: chen_gang_triones@163.com

Dian-zhong Luo, email: 13878802796@163.com

Keywords: esophageal carcinoma, DEMs, DEGs, TCGA, diagnosis

Received: November 08, 2016     Accepted: February 28, 2017     Published: March 09, 2017

ABSTRACT

Esophageal carcinoma (ESCA) is one of the most common malignancies worldwide, and its pathogenesis is complex. In this study, we identified differentially expressed miRNAs (DEMs) and genes (DEGs) of ESCA from The Cancer Genome Atlas (TCGA) database. The diagnostic values of DEMs were determined by receiver operating characteristic (ROC) analyses and validated based on data from Gene Expression Omnibus (GEO). The top five DEMs with the best diagnostic values were selected, and their potential targets were predicted by various in silico methods. These target genes were then identified among the DEGs from TCGA. Furthermore, the overlapping genes were subjected to protein-protein interaction (PPI) analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The miRNA-transcription factor (TF) regulatory relations were determined using CircuitsDB and TransmiR. Finally, the regulatory networks of miRNA-TF and miRNA-gene were constructed and analyzed. A total of 136 DEMs and 3541 DEGs were identified in ESCA. The top five DEMs with the highest area under the receiver operating characteristic curve (AUC) values were miRNA-93 (0.953), miRNA-21 (0.928), miRNA-4746 (0.915), miRNA-196a-1 (0.906) and miRNA-196a-2 (0.906). The combined AUC of these five DEMs was 0.985. The KEGG analysis with 349 overlapping genes showed that the calcium signaling pathway and the neuroactive ligand-receptor interaction were the most relevant pathways. The regulatory networks of miRNA-TF and miRNA-gene, including 38 miRNA-TF and 560 miRNA-gene pairs, were successfully established. Our findings may provide new insights into the molecular mechanisms of ESCA pathogenesis. Future research will aim to explore the role of novel miRNAs in the pathogenesis and improve the early diagnosis of ESCA.


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