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Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database.

ABSTRACT: Stomach adenocarcinoma (STAD) is the second leading cause of cancer death and a fuller understanding of its molecular basis is needed to develop new therapeutic targets. miRNA and mRNA data were downloaded from The Cancer Genome Atlas database, and the differentially expressed miRNAs and genes were identified. The target genes of differentially expressed miRNAs were screened by prediction tools. Furthermore, the biological function of these target genes was investigated. Several key miRNAs and their target genes were selected for validation using quantitative real-time polymerase chain reaction (qRT-PCR). The Gene Expression Omnibus (GEO) dataset was used to verify the expression of selected miRNAs and target genes. The diagnostic value of identified miRNAs and genes was accessed by receiver operating characteristic analysis. A total of 1248 differentially expressed genes were identified in STAD. Additionally, nine differentially expressed miRNAs were identified and 160 target genes of these nine miRNAs were identified via target gene detection. Interestingly, they were remarkably enriched in the calcium signaling pathway and bile secretion. qRT-PCR confirmed the expression of several key miRNAs and their target genes. The expression levels of hsa-miR-145-3p, hsa-miR-145-5p, ADAM12,ACAN,HOXC11 and MMP11 in the GEO database were compatible with the bioinformatics results. hsa-miR-139-5p, hsa-miR-145-3p and MMP11 have a potential diagnostic value for STAD. Differential expression of the mature form of miRNAs (hsa-miR-139-5p, hsa-miR-145-3p, hsa-miR-145-5p and hsa-miR-490-3p) and genes including ADAM12,ACAN,HOXC11 and MMP11 and calcium and bile secretion signaling pathways may play important roles in the development of STAD.

SUBMITTER: Liu J

PROVIDER: S-EPMC5794471 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database.

Liu Jixi J Liu Fang F Shi Yanfen Y Tan Huangying H Zhou Lei L

FEBS open bio 20180102 2

Stomach adenocarcinoma (STAD) is the second leading cause of cancer death and a fuller understanding of its molecular basis is needed to develop new therapeutic targets. miRNA and mRNA data were downloaded from The Cancer Genome Atlas database, and the differentially expressed miRNAs and genes were identified. The target genes of differentially expressed miRNAs were screened by prediction tools. Furthermore, the biological function of these target genes was investigated. Several key miRNAs and t ...[more]

PMID: 29435418

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Project description:BackgroundLung adenocarcinoma (LUAD) is one of the most common cancers worldwide. The etiology and pathophysiology of LUAD remain unclear. The aim of the present study was to identify the key genes, miRNAs and transcription factors (TFs) associated with the pathogenesis and prognosis of LUAD.MethodsThree gene expression profiles (GSE43458, GSE32863, GSE74706) of LUAD were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by GEO2R.The Gene Ontology (GO) terms, pathways, and protein-protein interactions (PPIs) of these DEGs were analyzed. Bases on DEGs, the miRNAs and TFs were predicted. Furthermore, TF-gene-miRNA co-expression network was constructed to identify key genes, miRNAs and TFs by bioinformatic methods. The expressions and prognostic values of key genes, miRNAs and TFs were carried out through The Cancer Genome Atlas (TCGA) database and Kaplan Meier-plotter (KM) online dataset.ResultsA total of 337 overlapped DEGs (75 upregulated and 262 downregulated) of LUAD were identified from the three GSE datasets. Moreover, 851 miRNAs and 29 TFs were identified to be associated with these DEGs. In total, 10 hub genes, 10 key miRNAs and 10 key TFs were located in the central hub of the TF-gene-miRNA co-expression network, and validated using The Cancer Genome Atlas (TCGA) database. Specifically, seven genes (PHACTR2, MSRB3, GHR, PLSCR4, EPB41L2, NPNT, FBXO32), two miRNAs (hsa-let-7e-5p, hsa-miR-17-5p) and four TFs (STAT6, E2F1, ETS1, JUN) were identified to be associated with prognosis of LUAD, which have significantly different expressions between LUAD and normal lung tissue. Additionally, the miRNA/gene co-expression analysis also revealed that hsa-miR-17-5p and PLSCR4 have a significant negative co-expression relationship (r=?0.33, P=1.67e-14) in LUAD.ConclusionsOur study constructed a regulatory network of TF-gene-miRNA in LUAD, which may provide new insights about the interaction between genes, miRNAs and TFs in the pathogenesis of LUAD, and identify potential biomarkers or therapeutic targets for LUAD.

Project description:Purpose:Stomach adenocarcinoma (STAD) is one of the most frequently diagnosed cancer in the world with both high mortality and high metastatic capacity. Therefore, the present study aimed to investigate novel therapeutic targets and prognostic biomarkers that can be used for STAD treatment. Materials and Methods:We acquired four original gene chip profiles, namely GSE13911, GSE19826, GSE54129, and GSE65801 from the Gene Expression Omnibus (GEO). The datasets included a total of 114 STAD tissues and 110 adjacent normal tissues. The GEO2R online tool and Venn diagram software were used to discriminate differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) enriched pathways were also performed for annotation and visualization with DEGs. The STRING online database was used to identify the functional interactions of DEGs. Subsequently, we selected the most significant DEGs to construct the protein-protein interaction (PPI) network and to reveal the core genes involved. Finally, the Kaplan-Meier Plotter online database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to analyze the prognostic information of the core DEGs. Results:A total of 114 DEGs (35 upregulated and 79 downregulated) were identified, which were abnormally expressed in the GEO datasets. GO analysis demonstrated that the majority of the upregulated DEGs were significantly enriched in collagen trimer, cell adhesion, and identical protein binding. The downregulated DEGs were involved in extracellular space, digestion, and inward rectifier potassium channel activity. Signaling pathway analysis indicated that upregulated DEGs were mainly enriched in receptor interaction, whereas downregulated DEGs were involved in gastric acid secretion. A total of 80 DEGs were screened into the PPI network complex, and one of the most important modules with a high degree was detected. Furthermore, 10 core genes were identified, namely COL1A1, COL1A2, FN1, COL5A2, BGN, COL6A3, COL12A1, THBS2, CDH11, and SERPINH1. Finally, the results of the prognostic information further demonstrated that all 10 core genes exhibited significantly higher expression in STAD tissues compared with that noted in normal tissues. Conclusion:The multiple molecular mechanisms of these novel core genes in STAD are worthy of further investigation and may reveal novel therapeutic targets and biomarkers for STAD treatment.

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Dataset Information

Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database.

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Identification of key miRNAs and genes associated with stomach adenocarcinoma from The Cancer Genome Atlas database.

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