Dataset Information

Bioinformatic identification of key genes and pathways that may be involved in the pathogenesis of HBV-associated acute liver failure.

ABSTRACT: In order to explore the molecular mechanisms behind the pathogenesis of acute liver failure (ALF) associated with hepatitis B virus (HBV) infection, the present study aimed to identify potential key genes and pathways involved using samples from patients with HBV-associated ALF. The GSE38941 array dataset was downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between 10 liver samples from 10 healthy donors and 17 liver specimens from 4 patients with HBV-associated ALF were analyzed using the Linear Models for Microarray Data package. Gene Ontology and KEGG pathway enrichment analyses of the DEGs were performed, followed by functional annotation of the genes and construction of a protein-protein interaction (PPI) network. Subnetwork modules were subsequently identified and analyzed. In total, 3142 DEGs were identified, of which 1755 were upregulated and 1387 were downregulated. The extracellular exosome, immune response, and inflammatory response pathways may potentially be used as biomarkers of ALF pathogenesis. In total, 17 genes (including CCR5, CXCR4, ALB, C3, VGEFA, and IGF1) were identified as hub genes in the PPI network and may therefore be potential marker genes for HBV-associated ALF.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6303483 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Bioinformatic identification of key genes and pathways that may be involved in the pathogenesis of HBV-associated acute liver failure.

Yang Yalan Y Zhong Zhaohui Z Ding Yubin Y Zhang Wanfeng W Ma Yang Y Zhou Li L

Genes & diseases 20180302 4

In order to explore the molecular mechanisms behind the pathogenesis of acute liver failure (ALF) associated with hepatitis B virus (HBV) infection, the present study aimed to identify potential key genes and pathways involved using samples from patients with HBV-associated ALF. The GSE38941 array dataset was downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between 10 liver samples from 10 healthy donors and 17 liver specimens from 4 patients with H ...[more]

PMID: 30591937

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Project description:BackgroundAcute liver failure (ALF) is a life-threatening complication that is relatively uncommon. ALF causes severe hepatocyte damage and necrosis, which can lead to liver dysfunction and even multi-organ failure. A growing body of evidence suggests that immune cell infiltration and some abnormally expressed genes are associated with ALF development. However, in ALF, they have yet to be thoroughly investigated.MethodsThe Gene Expression Omnibus (GEO) database was used to obtain microarray datasets such as GSE74000, GSE120652, GSE38941, and GSE14668, which were then examined via GEO2R to determine differentially expressed genes (DEGs) associated with ALF. Metascape was employed to annotate the underlined genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The mechanism of IGF1 in 2 different kinds of ALF including acetaminophen-induced ALF and hepatitis B virus (HBV)-induced ALF was studied using gene set enrichment analysis (GSEA). Next, immune cell infiltration was investigated and differentiated in ALF using CIBERSORT.ResultsSix genes (HAO2, IGF1, PLA2G7, SC5D, GNE, SLC1A1) were found to be abnormally expressed in the 2 distinct types of ALF i.e., acetaminophen-induced ALF and HBV-induced ALF. IGF1 was identified as a hub gene in ALF and was found to be associated with several developmental cascades including immune responses, inflammatory responses, and intracellular calcium homeostasis. Additionally, the number of CD4 naive T cells, CD8 T cells, and follicular helper T cells was increased in acetaminophen-induced ALF, whereas the number of activated NK cells, resting NK cells, and plasma cells was increased in HBV-induced ALF.ConclusionsThe present study determined a potential molecular target, namely IGF1, in acetaminophen-induced ALF and HBV-induced ALF, which may provide novel insights into the pathophysiology and management of ALF. Concurrently, the putative immunological pathways have been found.

Project description:Melanoma is the deadliest skin tumor and is prone to distant metastases. The incidence of melanoma has increased rapidly in the past few decades, and current trends indicate that this growth is continuing. This study was aimed to explore the molecular mechanisms of melanoma pathogenesis and discover underlying pathways and genes associated with melanoma. We used high-throughput expression data to study differential expression profiles of related genes in melanoma. The differentially expressed genes (DEGs) of melanoma in GSE15605, GSE46517, GSE7553, and the Cancer Genome Atlas (TCGA) datasets were analyzed. Differentially expressed genes (DEGs) were identified by paired t-test. Then the DEGs were performed cluster and principal component analyses and protein-protein interaction (PPI) network construction. After that, we analyzed the differential genes through bioinformatics and got hub genes. Finally, the expression of hub genes was confirmed in the TCGA databases and collected patient tissue samples. Total 144 up-regulated DEGs and 16 down-regulated DEGs were identified. A total of 17 gene ontology analysis (GO) terms and 11 pathways were closely related to melanoma. Pathway of pathways in cancer was enriched in 8 DEGs, such as junction plakoglobin (JUP) and epidermal growth factor receptor (EGFR). In the PPI networks, 9 hub genes were obtained, such as loricrin (LOR), filaggrin (FLG), keratin 5 (KRT5), corneodesmosin (CDSN), desmoglein 1 (DSG1), desmoglein 3 (DSG3), keratin 1 (KRT1), involucrin (IVL), and EGFR. The pathway of pathways in cancer and its enriched DEGs may play important roles in the process of melanoma. The hub genes of DEGs may become promising melanoma candidate genes. Five key genes FLG, DSG1, DSG3, IVL, and EGFR were identified in the TCGA database and melanoma tissues. The results suggested that FLG, DSG1, DSG3, IVL, and EGFR might play important roles and potentially be valuable in the prognosis and treatment of melanoma. These hub genes might well have clinical significance as diagnostic markers.

Dataset Information

Bioinformatic identification of key genes and pathways that may be involved in the pathogenesis of HBV-associated acute liver failure.

Publications

Bioinformatic identification of key genes and pathways that may be involved in the pathogenesis of HBV-associated acute liver failure.

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