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pmid:31114367
Identification of a transcription factor-microRNA network in esophageal adenocarcinoma through bioinformatics analysis and validation through qRT-PCR.
Di Chen · Tong Lu · Junying Tan · Kun Zhao · Yuli Li · Wenjie Zhao · Hao Li · Qiuyue Wang · Yuanyong Wang · Liangzhou Wei
Cancer management and research · 2019 doi:10.2147/CMAR.S201274
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Experiment
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Complete file
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This study investigated the potential transcription factor (TF)-related molecular mechanisms of EAC by using bioinformatics analysis and qRT-PCR validation. Methods: Expression profile datasets for mRNAs (GSE92396, GSE13898, GSE26886 and GSE1420) and miRNAs (GSE16456) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. Then, a TF-miRNA-mRNA network was constructed based on bioinformatics data from the TRRUST, TRED and miRTarBase database. Furthermore, overall survival analysis for the mRNAs and miRNAs in the TF-miRNA-mRNA network was performed with data from TCGA, and qRT-PCR was used to validate the results. Results: A total of 294 overlapping DEGs were identified in EAC tissues compared to normal tissues, including 181 downregulated and 113 upregulated genes. Then, 16 TFs that could target the DEGs and were related to cancer were predicted based on public databases, and 41 DEGs that could be targeted were identified as key genes. Additionally, 12 DEMs were predicted through miRTarBase to be associated with the key genes, and TP53-(miR-125b)-ID2 and JUN-(miR-30a)-IL1A from the TF-miRNA-mRNA network were identified to potentially play significant roles in EAC. Furthermore, CCL20, IL1A, ABCC3, hsa-miR-23b, and hsa-miR-191, which are involved in the TF-miRNA-mRNA network, were found to be significantly associated with patient survival in EAC. Finally, the expression of a miRNA-mRNA pair (hsa-miR-30a-5p and IL1A) was revealed to be correlated with prognosis. Conclusion: In this study, a TF-miRNA-mRNA network was constructed to analyze the potential molecular mechanisms of EAC. Key genes and miRNAs associated with patient survival were identified, which may reveal promising approaches for EAC diagnosis and therapy.", "claims": [{"id": "claim-method", "statement": "To verify the results obtained thus far, data for 89 EAC tissue samples and the clinical data of the patients were downloaded from TCGA, and the prognostic value of the key genes and miRNAs was identified by Kaplan-Meier analysis. The survival package in R software was used for survival analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31114367", "locator": "sections[8] \"Survival analysis validation\" paragraph 2", "quote": "To verify the results obtained thus far, data for 89 EAC tissue samples and the clinical data of the patients were downloaded from TCGA, and the prognostic value of the key genes and miRNAs was identified by Kaplan-Meier analysis. 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"rows": [["Relationship", "Number of pairs/sets", "Number of TFs", "Number of key genes", "Number of miRNAs"], ["TF-key gene", "97", "16", "41", "-"], ["miRNA-key gene", "12", "-", "7", "12"], ["TF-miRNA-key gene", "2", "2", "2", "2"]], "row_count": 4, "column_count": 5, "numeric_cells": 10, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T0003"}}, {"id": "asset:table:pmid:31114367:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:5b537b2eda1bb613850cee3380dc5320484edd67dce2875b09b16fd1225c6ffc", "bytes": 1538, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#T0004", "version": null, "note": "GO terms of key genes", "structure": {"pmcid": "PMC6489589", "section_index": 14, "section_title": "Functional and pathway analysis of key genes", "row_count": 21, "column_count": 4}, "table": {"label": "Table 4", "caption": "GO terms of key genes", "rows": [["", "GO terms", "Number of enriched genes", "P-value"], ["Biological process", "GO:0006954-inflammatory response", "9", "2.56E-06"], ["", "GO:0022617-extracellular matrix disassembly", "5", "3.13E-05"], ["", "GO:0043123-positive regulation of I-kappaB kinase/NF-kappaB signaling", "5", "5.69 E-04"], ["", "GO:0008544-epidermis development", "4", "1.08 E-03"], ["", "GO:0001649-osteoblast differentiation", "4", "1.93 E-03"], ["", "GO:0008285-negative regulation of cell proliferation", "6", "2.37 E-03"], ["", "GO:0043066-negative regulation of apoptotic process", "6", "4.30 E-03"], ["", "GO:0031424-keratinization", "3", "5.82 E-03"], ["", "GO:0018149-peptide cross-linking", "3", "6.30 E-03"], ["", "GO:0002248~connective tissue replacement involved in inflammatory response wound healing", "2", "9.50 E-03"], ["", "GO:0030574-collagen catabolic process", "3", "1.02 E-02"], ["Cellular component", "GO:0005615-extracellular space", "17", "8.33E-09"], ["", "GO:0005576-extracellular region", "18", "1.38E-08"], ["", "GO:0070062-extracellular exosome", "21", "3.26E-07"], ["", "GO:0005578-proteinaceous extracellular matrix", "6", "2.86E-04"], ["", "GO:0001533-cornified envelope", "3", "4.57E-03"], ["Molecular function", "GO:0005125-cytokine activity", "6", "5.03E-05"], ["", "GO:0008083-growth factor activity", "5", "5.17E-04"], ["", "GO:0005515-protein binding", "31", "1.24E-03"], ["", "GO:0004175-endopeptidase activity", "3", "6.90E-03"]], "row_count": 21, "column_count": 4, "numeric_cells": 60, "header_rows": 1, "locator": "section[14]/table-wrap[1]#T0004"}}, {"id": "asset:table:pmid:31114367:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ee60491e2865b7a94f4acb2de27ed85995440e6a81081e2e4319b270ec25292d", "bytes": 515, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[2]#T0005", 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