Dataset Information

Identification of key regulators of pancreatic ductal adenocarcinoma using bioinformatics analysis of microarray data.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and its etiology remains largely unknown. This study aimed to screen a panel of key genes and to identify their potential impact on the molecular pathways associated with the development of PDAC. Four gene expression profiles, GSE28735, GSE15471, GSE102238, and GSE43795, were downloaded from the Gene Expression Omnibus (GEO) database. The intersection of the differentially expressed genes (DEGs) in each dataset was obtained using Venn analysis. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis were subsequently carried out. To screen for hub genes, a protein-protein interaction (PPI) network was constructed.The intersection of the DEGs revealed 7 upregulated and 9 downregulated genes. Upon relaxation of the selection criteria, 58 upregulated and 32 downregulated DEGs were identified. The top 5 biological processes identified by GO analysis involved peptide cross-linking, extracellular matrix (ECM) disassembly, regulation of the fibroblast growth factor receptor signaling pathway, mesoderm morphogenesis, and lipid digestion. The results of KEGG analysis revealed that the DEGs were significantly enriched in pathways involved in protein digestion and absorption, ECM-receptor interaction, pancreatic secretion, and fat digestion and absorption. The top ten hub genes were identified based on the PPI network.In conclusion, the identified hub genes may contribute to the elucidation of the underlying molecular mechanisms of PDAC and serve as promising candidates that can be utilized for the early diagnosis and prognostic prediction of PDAC. However, further experimental validation is required to confirm these results.

SUBMITTER: Li N

PROVIDER: S-EPMC6336631 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Identification of key regulators of pancreatic ductal adenocarcinoma using bioinformatics analysis of microarray data.

Li Nan N Zhao Xin X You Shengyi S

Medicine 20190101 2

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and its etiology remains largely unknown. This study aimed to screen a panel of key genes and to identify their potential impact on the molecular pathways associated with the development of PDAC. Four gene expression profiles, GSE28735, GSE15471, GSE102238, and GSE43795, were downloaded from the Gene Expression Omnibus (GEO) database. The intersection of the differentially expressed genes (DEGs) in each dataset wa ...[more]

PMID: 30633213

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Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most complicated and fatally pathogenic human malignancies. Therefore, there is an urgent need to improve our understanding of the underlying molecular mechanism that drives the initiation, progression, and metastasis of PDAC. The aim of the present study was to identify the key genes and signaling pathways associated with PDAC using bioinformatics analysis. Four transcriptome microarray datasets (GSE15471, GSE55643, GSE62165 and GSE91035) were acquired from Gene Expression Omnibus datasets, which included 226 PDAC samples and 65 normal pancreatic tissue samples. We screened differentially expressed genes (DEGs) with GEO2R and investigated their biological function by Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analysis. The overall survival data was obtained from UALCAN, which calculated the data shared with The Cancer Genome Atlas. In addition, a protein-protein interaction (PPI) network of the DEGs was constructed by STRING and Cytoscape software. The four sets of DEGs exhibited an intersection consisting of 205 genes (142 up-regulated and 63 down-regulated), which may be associated with PDAC. GO analysis showed that the 205 DEGs were significantly enriched in the plasma membrane, cell adhesion molecule activity and the Energy pathways, and glycine, serine, threonine metabolism were the most enriched pathways according to KEGG pathway analysis. Kaplan-Meier survival analysis revealed that 22 of 205 common genes were significantly associated with the overall survival of pancreatic cancer patients. In the PPI network and sub-network, DKK1 and HMGA2 were considered as hub genes with high connectivity degrees. DKK1 and HMGA2 are strongly associated with WNT3A and TP53 separately, which indicates that they may play an important role in the Wnt and P53 signaling pathways. Using integrated bioinformatics analysis, we identified DKK1 and HMGA2 as candidate genes in PDAC, which may improve our understanding of the mechanisms of the pathogenesis and integration; the two genes may be therapeutic targets and prognostic markers for PDAC.

Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) develops rapidly and has a poor prognosis. It has been demonstrated that pancreatic ductal adenocarcinoma and chronic pancreatitis (CP) have a close connection. However, the underlying mechanisms for chronic pancreatitis transforming into pancreatic ductal adenocarcinoma are still unclear. The purpose of this study was to identify real hub genes in the development of chronic pancreatitis and pancreatic ductal adenocarcinoma. Methods: RNA-seq data of chronic pancreatitis and pancreatic ductal adenocarcinoma were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to construct a gene co-expression network between chronic pancreatitis and pancreatic ductal adenocarcinoma. GEO2R and a Venn diagram were used to identify differentially expressed genes. Then visualized networks were constructed with ClueGO, and modules of PPI network were calculated by MCODE plugin. Further validation of the results was carried out in two additional cohorts. Analyses of CEL-coexpressed genes and regulators including miRNAs and transcription factors were performed by using the corresponding online web tool. Finally, the influence of CEL in the tumor immune microenvironment (TIME) was assessed by immune contextual analysis. Results: With the help of WGCNA and GEO2R, four co-expression modules and six hub genes were identified, respectively. ClueGO enrichment analysis and MCODE cluster analysis revealed that the dysfunctional transport of nutrients and trace elements might contribute to chronic pancreatitis and pancreatic ductal adenocarcinoma development. The real hub gene CEL was identified with a markedly low expression in pancreatic ductal adenocarcinoma in external validation sets. According to the miRNA-gene network construction, hsa-miR-198 may be the key miRNA. A strong correlation exists between CEL and TIME after an evaluation of the influence of CEL in TIME. Conclusion: Our study revealed the dysfunctional transport of nutrients and trace elements may be common pathogenesis of pancreatic ductal adenocarcinoma and chronic pancreatitis. Examination on these common pathways and real hub genes may shed light on the underlying mechanism.

Project description:Pancreatitis is a type of inflammation in the pancreas, which frequently occurs due to alcohol and gallstones. The present study aimed to identify pancreatitis‑associated microRNAs (miRNAs) by analyzing the microarray of GSE24279. GSE24279 was downloaded from the Gene Expression Omnibus, composed of a collective of 27 pancreatitis and 22 normal control samples. The differentially expressed miRNAs (DE‑miRNAs) in pancreatitis samples were screened using the Limma package in Bioconductor. Subsequently, target genes of the DE‑miRNAs were predicted using the miRecords and miRWalk databases. Their potential functions were analyzed by functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery online tool. Finally, pancreatitis‑associated genes among the target genes identified were searched using the Comparative Toxicogenomics Database, and a regulatory network of pancreatitis‑associated genes and their target miRNAs were constructed using Cytoscape software. A total 14 upregulated and 39 downregulated miRNAs were identified in pancreatitis samples compared with control samples and 290 target genes of DE‑miRNAs were determined. Cyclin D1 (CCND1), v‑akt murine thymoma viral oncogene homolog 2 (AKT2), cyclin‑dependent kinase 6 (CDK6) and SMAD family member 2 (SMAD2) were involved in the pathway of pancreatic cancer. Among the target genes, 279 genes were pancreatitis‑associated genes, which in turn were targeted by 37 miRNAs in the regulatory network. Hsa‑miR‑15a, hsa‑miR‑16, hsa‑miR‑155, hsa‑miR‑375 and hsa‑miR‑429 in particular may be involved in pancreatitis by targeting genes in the regulatory network, including hsa‑miR‑15a→CCND1, hsa‑miR‑16→CCND1, hsa‑miR‑155→CCND1/SMAD2, hsa‑miR‑375→AKT2/CDK6 and hsa‑miR‑429→CCND1. The above miRNAs and their targets may contribute to the pathogenesis of pancreatitis; therefore, they may be potential therapeutic targets.

Dataset Information

Identification of key regulators of pancreatic ductal adenocarcinoma using bioinformatics analysis of microarray data.

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Identification of key regulators of pancreatic ductal adenocarcinoma using bioinformatics analysis of microarray data.

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