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An integrated analysis of key microRNAs, regulatory pathways and clinical relevance in bladder cancer.

ABSTRACT: Objective:The aim of this study was to identify the key microRNAs (miRNAs) and their regulatory networks in bladder cancer (BC). Materials and methods:Three miRNA and three gene expression microarray datasets were downloaded for analysis from Gene Expression Omnibus database. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were accessed by the use of GEO2R. Gene ontology process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed by using the Database for Annotation, Visualization and Integrated Discovery program. Protein-protein interaction (PPI) and miRNA-mRNA regulatory networks were established by using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape tool. Besides, the results and clinical significance were validated in The Cancer Genome Atlas (TCGA) dataset. Results:A total of 18 significant DEMs, 121 upregulated DEGs and 199 downregulated DEGs were identified. Functional enrichment analysis showed that significant DEGs were related to cell cycle and MAPK pathway in BC. Key DEGs such as CDK1, CCNB1, VGL and PRKCA were found as the hub genes in PPI networks. TCGA analysis supported our results, and the miRNAs were correlated with the pathological stages and survival of BC patients. Conclusion:In this study, we found 18 DEMs that may play key roles in the regulatory networks of BC. The higher expression of miR-99a, miR-100, miR-125b, miR-145, miR-214 and miR-487b or the lower expression of miR-138 and miR-200a can indicate poor survival in the prognosis of BC. Further experimental studies are required to test our results.

SUBMITTER: Li D

PROVIDER: S-EPMC5975595 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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An integrated analysis of key microRNAs, regulatory pathways and clinical relevance in bladder cancer.

Li Dongyang D Hao Xuanyu X Song Yongsheng Y Song Yongsheng Y

OncoTargets and therapy 20180524

<h4>Objective</h4>The aim of this study was to identify the key microRNAs (miRNAs) and their regulatory networks in bladder cancer (BC).<h4>Materials and methods</h4>Three miRNA and three gene expression microarray datasets were downloaded for analysis from Gene Expression Omnibus database. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were accessed by the use of GEO2R. Gene ontology process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment ana ...[more]

PMID: 29872319

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Project description:Breast cancer (BC) is the leading malignancy in women worldwide, yet relatively little is known about the genes and signaling pathways involved in BC tumorigenesis and progression. The present study aimed to elucidate potential key candidate genes and pathways in BC. Five gene expression profile data sets (GSE22035, GSE3744, GSE5764, GSE21422 and GSE26910) were downloaded from the Gene Expression Omnibus (GEO) database, which included data from 113 tumorous and 38 adjacent non?tumorous tissue samples. Differentially expressed genes (DEGs) were identified using t?tests in the limma R package. These DEGs were subsequently investigated by pathway enrichment analysis and a protein?protein interaction (PPI) network was constructed. The most significant module from the PPI network was selected for pathway enrichment analysis. In total, 227 DEGs were identified, of which 82 were upregulated and 145 were downregulated. Pathway enrichment analysis results revealed that the upregulated DEGs were mainly enriched in 'cell division', the 'proteinaceous extracellular matrix (ECM)', 'ECM structural constituents' and 'ECM?receptor interaction', whereas downregulated genes were mainly enriched in 'response to drugs', 'extracellular space', 'transcriptional activator activity' and the 'peroxisome proliferator?activated receptor signaling pathway'. The PPI network contained 174 nodes and 1,257 edges. DNA topoisomerase 2?a, baculoviral inhibitor of apoptosis repeat?containing protein 5, cyclin?dependent kinase 1, G2/mitotic?specific cyclin?B1 and kinetochore protein NDC80 homolog were identified as the top 5 hub genes. Furthermore, the genes in the most significant module were predominantly involved in 'mitotic nuclear division', 'mid?body', 'protein binding' and 'cell cycle'. In conclusion, the DEGs, relative pathways and hub genes identified in the present study may aid in understanding of the molecular mechanisms underlying BC progression and provide potential molecular targets and biomarkers for BC.

Project description:The aim of the present study was to identify potential key genes associated with the progression and prognosis of colorectal cancer (CRC). Differentially expressed genes (DEGs) between CRC and normal samples were screened by integrated analysis of gene expression profile datasets, including the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to identify the biological role of DEGs. In addition, a protein‑protein interaction network and survival analysis were used to identify the key genes. The profiles of GSE9348, GSE22598 and GSE113513 were downloaded from the GEO database. A total of 405 common DEGs were identified, including 236 down‑ and 169 upregulated. GO analysis revealed that the downregulated DEGs were mainly enriched in 'detoxification of copper ion' [biological process, (BP)], 'oxidoreductase activity, acting on CH‑OH group of donors, NAD or NADP as acceptor' [molecular function, (MF)] and 'brush border' [cellular component, (CC)]. Upregulated DEGs were mainly involved in 'nuclear division' (BP), 'snoRNA binding' (MF) and 'nucleolar part' (CC). KEGG pathway analysis revealed that DEGs were mainly involved in 'mineral absorption', 'nitrogen metabolism', 'cell cycle' and 'caffeine metabolism'. A PPI network was constructed with 268 nodes and 1,027 edges. The top one module was selected, and it was revealed that module‑related genes were mainly enriched in the GO terms 'sister chromatid segregation' (BP), 'chemokine activity' (MF), and 'condensed chromosome (CC)'. The KEGG pathway was mainly enriched in 'cell cycle', 'progesterone‑mediated oocyte maturation', 'chemokine signaling pathway', 'IL‑17 signaling pathway', 'legionellosis', and 'rheumatoid arthritis'. DNA topoisomerase II‑α (TOP2A), mitotic arrest deficient 2 like 1 (MAD2L1), cyclin B1 (CCNB1), checkpoint kinase 1 (CHEK1), cell division cycle 6 (CDC6) and ubiquitin conjugating enzyme E2 C (UBE2C) were indicated as hub genes. Furthermore, survival analysis revealed that TOP2A, MAD2L1, CDC6 and CHEK1 may serve as prognostic biomarkers in CRC. The present study provided insights into the molecular mechanism of CRC that may be useful in further investigations.

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Project description:Cell division cycle associated 8 (CDCA8) overexpression is detected in various malignant tumors and closely associated with tumor growth. However, the correlations of CDCA8 expression with clinicopathological factors and prognosis of bladder cancer (BC) remain unclear. The purpose of this study was to identify the expression of CDCA8 and its clinical relevance in BC patients.GEO datasets were employed to obtain CDCA8 expression data and its clinical information in BC samples. Real-time PCR (RT-PCR) was performed to detect the expression of CDCA8 in BC and the adjacent normal tissues. Nonpaired t test was used to statistically analyze the difference between the 2 groups. Cox univariable and multivariable analyses of overall survival (OS) and cancer specific survival (CSS) among BC patients were performed. Biological processes or signaling pathways that might mediate the activity of CDCA8 in BC were analyzed.CDCA8 levels were significantly higher in BC (8.870?±?0.08281 vs 7.472?±?0.07035, P?<?.0001). CDCA8 expression was significantly associated with tumor progression (P?=?.001), T stage (P?<?.0001), N stage (P?=?.013), and grade (P?<?.0001). Higher expression of CDCA8 predicted poor cancer-specific survival (P?<?.0001, HR?=?0.2752, 95% CI:0.1364-0.5554) and overall survival (P?<?.0001, HR?=?0.4270, 95% CI: 0.2630-0.6930) in patients with BC. Cox univariable and multivariable analyses showed that intravesical therapy, N stage and progression were the independent influence factors of overall survival among bladder cancer patients, CDCA8 expression, tumor grade and progression were the independent influence factors of cancer specific survival among bladder cancer patients. The results of GSEA indicated that CDCA8-regulated gene sets associated with spermatogenesis, G2M checkpoint, E2F targets, Myc targets, mTORC1 signaling, mitotic spindle angiogenesis, PI3K/AKT/mTOR signaling, cholesterol homeostasis and glycolysis. Finally, RT-PCR results confirmed that CDCA8 expression was upregulated in BC (P?=?.0039).CDCA8 is overexpressed in BC and its high levels are correlated with poor clinicopathological features of BC patients. Therefore, CDCA8 may act as a novel prognostic marker and therapeutical target in the diagnosis and treatment of patients with BC.

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An integrated analysis of key microRNAs, regulatory pathways and clinical relevance in bladder cancer.

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An integrated analysis of key microRNAs, regulatory pathways and clinical relevance in bladder cancer.

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