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Transcriptome analyses identify hub genes and potential mechanisms in adenoid cystic carcinoma.

ABSTRACT: Adenoid cystic carcinoma (ACC) is one of the most frequent malignancies of salivary glands. The objective of this study was to identify key genes and potential mechanisms during ACC samples.The gene expression profiles of GSE88804 data set were downloaded from Gene Expression Omnibus. The GSE88804 data set contained 22 samples, including 15 ACC samples and 7 normal salivary gland tissues. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were constructed, and protein-protein interaction network of differentially expressed genes (DEGs) was performed by Cytoscape. The top 10 hub genes were analyzed based on Gene Expression Profiling Interactive Analysis. Then, DEGs between ACC samples and normal salivary gland samples were analyzed by gene set enrichment analysis. Furthermore, miRTarBase and Cytoscape were used for visualization of miRNA-mRNA regulatory network. KEGG pathway analysis was undertaken using DIANA-miRPath v3.0.In total, 382 DEGs were identified, including 119 upregulated genes and 263 downregulated genes. GO analysis showed that DEGs were mainly enriched in extracellular matrix organization, extracellular matrix, and calcium ion binding. KEGG pathway analysis showed that DEGs were mainly enriched in p53 signaling pathway and salivary secretion. Expression analysis and survival analysis showed that ANLN, CCNB2, CDK1, CENPF, DTL, KIF11, and TOP2A are all highly expressed, which all may be related to poor overall survival. Predicted miRNAs of 7 hub DEGs mainly enriched in proteoglycans in cancer and pathways in cancer.This study indicated that identified DEGs and hub genes might promote our understanding of molecular mechanisms, which might be used as molecular targets or diagnostic biomarkers for ACC.

SUBMITTER: Liu HB

PROVIDER: S-EPMC6959903 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Transcriptome analyses identify hub genes and potential mechanisms in adenoid cystic carcinoma.

Liu Hong-Bing HB Huang Guan-Jiang GJ Luo Meng-Si MS

Medicine 20200101 2

Adenoid cystic carcinoma (ACC) is one of the most frequent malignancies of salivary glands. The objective of this study was to identify key genes and potential mechanisms during ACC samples.The gene expression profiles of GSE88804 data set were downloaded from Gene Expression Omnibus. The GSE88804 data set contained 22 samples, including 15 ACC samples and 7 normal salivary gland tissues. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were c ...[more]

PMID: 31914060

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Project description:Adenoid cystic carcinoma (AdCC) of the head and neck originates from salivary glands, with high risks of recurrence and metastasis that account for the poor prognosis of patients. The purpose of this research was to identify key genes related to AdCC for further investigation of their diagnostic and prognostic significance. In our study, the AdCC sample datasets GSE36820, GSE59702 and GSE88804 from the Gene Expression Omnibus (GEO) database were used to explore the abnormal coexpression of genes in AdCC compared with their expression in normal tissue. A total of 115 DEGs were obtained by screening with GEO2R and FunRich software. According to functional annotation analysis using Enrichr, these DEGs were mainly enriched in the SOX2, AR, SMAD and MAPK signaling pathways. A protein-protein network of the DEGs was established by the Search Tool for the Retrieval of Interacting Genes (STRING) and annotated through the WEB-based Gene SeT AnaLysis Toolkit (WebGestalt) and was shown to be enriched with proteins involved in cardiac muscle cell proliferation and extracellular matrix organization. A Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that ITGA9, LAMB1 and BAMBI were associated with the PI3K-Akt and TGF-β pathways. Furthermore, 36 potential target miRNAs were identified by the OncomiR and miRNA Pathway Dictionary Database (miRPathDB). In conclusion, SLC22A3, FOXP2, Cdc42EP3, COL27A1, DUSP1 and HSPB8 played critical roles according to the enrichment analysis; ITGA9, LAMB1 and BAMBI were involved in significant pathways according to the KEGG analysis; ST3Gal4 is a pivotal component of the PPI network of all the DEGs obtained; SPARC, COL4A2 and PRELP were highly related to multiple malignancies in pan-cancer research; hsa-miR-29-3p, hsa-miR-132-3p and hsa-miR-708-5p were potential regulators in AdCC. The involved pathways, biological processes and miRNAs have been shown to play significant roles in the genesis, growth, invasion and metastasis of AdCC. In this study, these identified DEGs were considered to have a potential influence on AdCC but have not been studied in this disease. The analysis results promote our understanding of the molecular mechanisms and biological processes of AdCC, which might be useful for targeted therapy or diagnosis.

Project description:Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. Figla, GDF9, Nobox, and Pou51 were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of Foxo1, Inha, and Taf4b was significantly de-creased at 20 W. Ccnd2 and Igf1 expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, Ccnd2 and Igf1, were identified as the major targets of many miRNAs (p < 0.05), and Fshr and Foxo3 interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with Piwil2, and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of Ccnd2 and Igf1 is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.

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Transcriptome analyses identify hub genes and potential mechanisms in adenoid cystic carcinoma.

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Transcriptome analyses identify hub genes and potential mechanisms in adenoid cystic carcinoma.

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