scholarly journals Gene Set Enrichment Analysis and Ingenuity Pathway Analysis to verify the impact on Wnt Signaling Pathway in Taodan Granules Treated Psoriasis

Author(s):  
Ying Luo ◽  
Ying Zhang ◽  
Shuang-yi Yin ◽  
Yue Luo ◽  
Xiao-jie Ding ◽  
...  

Abstract Background: Taodan granules (TDGs), traditional Chinese herbals, are effective in treating psoriasis. However, mechanisms of TDGs remain indistinct. The current study aims to indicate the molecular mechanisms of TDGs in treating psoriasis.Methods: Primarily, transcriptional profiling was applied to identify differentially expression genes (DEGs). The following was that we used Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analysis for functional enrichment analysis. Eventually, RT-PCR was performed to validation. Results: The results revealed that TDGs could regulated the Wnt signaling pathway to ameliorate skin lesions of imiquimod (IMQ)-induced psoriatic mouse models. IPA core network associated with Wnt signaling pathways in TDGs for psoriasis was established. Thereinto zeste homolog (EZH) 2, CTNNB1, TP63, and WD repeat domain (WDR) 5 could be considered as upstream genes in the Wnt signaling pathway.Conclusions: The Wnt signaling pathway with these above upstream genes might be potential therapeutic targets of TDGs for psoriasis.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Siqing Sun ◽  
Yutao Wang ◽  
Jianfeng Wang ◽  
Jianbin Bi

Abstract Background The Wnt signaling pathway is core to the growth of bladder tumors. Epithelial-to-mesenchymal transition (EMT) is significant for bladder tumor metastasis. Nevertheless, the relationship between the Wnt signaling pathway, outcomes of bladder cancer (BLCA), and the specific mechanisms driving immune infiltration have not been studied. Methods We obtained Wnt pathway-related gene mRNA and clinicopathological data from the Cancer Genome Atlas (TCGA). We obtained 34 genes that were greatly correlated with outcome using univariate Cox regression analysis and conducted a completely randomized data t-test to perform clinical staging. According to the single-sample gene set enrichment analysis (ssGSEA), the weighted correlation network analysis (WGCNA) was applied to identify relevant biological functions. Various subtypes were identified using consensus cluster analysis. Univariate Cox regression and least absolute shrinkage sum selection operator–Cox regression algorithm analysis were conducted on TCGA and Gene Expression Omnibus data to identify risk characteristics. The Kaplan–Meier method and receiver running feature curves were adopted to calculate overall survival. Single-sample gene set enrichment analysis (ssGSEA) was adopted for the assessment of the degree of immune infiltration. Then, we demonstrated the relationship between PPP2CB and EMT function in two cell lines. Results Thirty-four Wnt signaling pathway-related genes were risk factors for BLCA outcome, and their expression levels differed by clinical stage. The co-expression of WGCNA showed the relationship between the Wnt signaling pathway and biological functions and was closely associated with EMT. We divided BLCA patients into two subtypes using consensus clustering. Survival curves and clinical analysis showed that the Wnt pathway enriched group had worse outcomes. The Wnt signature showed the significance of the outcome for MAPK10, PPP2CB, and RAC3. Based on these genes, the degree of immune infiltration was evaluated. Cell function experiments suggested that PPP2CB drives the proliferation and migration of BLCA cells. Conclusion We found that Wnt signaling pathway-related genes can be used as prognostic risk factors for BLCA, and the Wnt signaling pathway is a cancer-promoting signaling pathway associated with EMT. We identified three critical genes: MAPK10, RAC3, and PPP2CB. The genes in these three Wnt signaling pathways are associated with tumor cell EMT and immune cell infiltration. The most important finding was that these three genes were independent prognostic factors for BLCA.


2021 ◽  
Author(s):  
Siqing Sun ◽  
Yutao Wang ◽  
Jianfeng Wang ◽  
Jianbin Bi

Abstract BackgroundThe Wnt signaling pathway is core to the growth of bladder tumors. Epithelial-to-mesenchymal transition (EMT) is significant for bladder tumor metastasis. Nevertheless, the relationship between the Wnt signaling pathway, outcomes of bladder cancer (BLCA), and the specific mechanisms driving immune infiltration have not been studied.MethodsWe obtained Wnt pathway-related gene mRNA and clinicopathological data from the Cancer Genome Atlas (TCGA). We obtained 34 genes that were greatly correlated with outcome using univariate Cox regression analysis and conducted a completely randomized data t-test to perform clinical staging. According to the single-sample gene set enrichment analysis (ssGSEA), the weighted correlation network analysis (WGCNA) was applied to identify relevant biological functions. Various subtypes were identified using consensus cluster analysis. Univariate Cox regression and least absolute shrinkage sum selection operator–Cox regression algorithm analysis were conducted on TCGA and Gene Expression Omnibus data to identify risk characteristics. The Kaplan–Meier method and receiver running feature curves were adopted to calculate overall survival. Single-sample gene set enrichment analysis (ssGSEA) was adopted for the assessment of the degree of immune infiltration. Then, we demonstrated the relationship between PPP2CB and EMT function in two cell lines. ResultsThirty-four Wnt signaling pathway-related genes were risk factors for BLCA outcome, and their expression levels differed by clinical stage. The co-expression of WGCNA showed the relationship between the Wnt signaling pathway and biological functions and was closely associated with EMT. We divided BLCA patients into two subtypes using consensus clustering. Survival curves and clinical analysis showed that the Wnt pathway enriched group had worse outcomes. The Wnt signature showed the significance of the outcome for MAPK10, PPP2CB, and RAC3. Based on these genes, the degree of immune infiltration was evaluated. Cell function experiments suggested that PPP2CB drives the proliferation and migration of BLCA cells.ConclusionWe found that Wnt signaling pathway-related genes can be used as prognostic risk factors for BLCA, and the Wnt signaling pathway is a cancer-promoting signaling pathway associated with EMT. We identified three critical genes: MAPK10, RAC3, and PPP2CB. The genes in these three Wnt signaling pathways are associated with tumor cell EMT and immune cell infiltration. The most important finding was that these three genes were independent prognostic factors for BLCA.


2020 ◽  
Author(s):  
Chen Xu ◽  
Ling-bing Meng ◽  
Yu Xiao ◽  
Yong Qiu ◽  
Ying-jue Du ◽  
...  

Abstract Background Osteoarthritis (OA) is a chronic, progressive, inflammatory, degenerative disease, which has become an osteoarthropathy that seriously affects physical health and quality of life of elderly people. However, the etiology and pathogenesis of OA remains unclear. Therefore, the study purposed to utilize bioinformatics technology to perform identification and functional enrichment analysis of differentially expressed genes in osteoarthritis. Method The main methods of this study consist of access to microarray data (GSE82107 and GSE55235), identification of differently expressed genes (DEGs) by GEO2R between OA and normal synovium samples, enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) by Gene Set Enrichment Analysis (GSEA), construction and analysis of protein-protein interaction (PPI) network, significant module and hub genes. Result A total of 300 DEGs were identified, consisting of 64 up-regulated genes and 11 down-regulated genes in OA samples compared to normal synovium tissues. Gene set enrichment analysis of DEGs provided a comprehensive overview of some major pathophysiological mechanisms in OA: cellular response to hydrogen peroxide, P53 signaling pathway and so on. The study also built the PPI network, and a total of 10 key genes were identified: CYR61, PENK, GOLM1, DUSP1, ATF3, STC2, FOSB, PRSS23, TF, and TNC. Conclusion DEGs exists between OA patients and normal cartilage tissue, which may be involved in the related mechanism of OA development, especially cellular response to hydrogen peroxide and CYR61.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shuang Gao ◽  
Ye Jin ◽  
Hongmei Zhang

WNT signaling pathway inhibitor Dickkopf-1 (DKK1) is related to cancer progression; however, its diagnostic and prognostic potential have not been investigated in a pan-cancer perspective. In this study, multiple bioinformatic analyses were conducted to evaluate therapeutic value of DKK1 in human cancers. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project served as data resources. The Wilcoxon rank test was performed to evaluate the expression difference of DKK1 between cancer tissues and normal tissues. A Kaplan-Meier curve and Cox regression were used for prognosis evaluation. Single-sample gene set enrichment analysis (ssGSEA) was used to evaluate the association of DKK1 expression with the immune cell infiltration. The potential function of DKK1 was explored by STRING and clusterProfiler. We found that the expression level of DKK1 is significantly different in different cancer types. Importantly, we demonstrated that DKK1 is an independent risk factor in ESCA, LUAD, MESO, and STAD. Further analysis revealed that DKK1 had a large effect on the immune cell infiltration and markers of certain immune cells, such as Th1 and Th2 cells. PPI network analysis and further pathway enrichment analysis indicated that DKK1 was mainly involved in the WNT signaling pathway. Our findings suggested that DKK1 might serve as a marker of prognosis for certain cancers by affecting the WNT signaling pathway and tumor immune microenvironment.


2019 ◽  
Vol 8 (10) ◽  
pp. 1580 ◽  
Author(s):  
Kyoung Min Moon ◽  
Kyueng-Whan Min ◽  
Mi-Hye Kim ◽  
Dong-Hoon Kim ◽  
Byoung Kwan Son ◽  
...  

Ninety percent of patients with scrub typhus (SC) with vasculitis-like syndrome recover after mild symptoms; however, 10% can suffer serious complications, such as acute respiratory failure (ARF) and admission to the intensive care unit (ICU). Predictors for the progression of SC have not yet been established, and conventional scoring systems for ICU patients are insufficient to predict severity. We aimed to identify simple and robust indicators to predict aggressive behaviors of SC. We evaluated 91 patients with SC and 81 non-SC patients who were admitted to the ICU, and 32 cases from the public functional genomics data repository for gene expression analysis. We analyzed the relationships between several predictors and clinicopathological characteristics in patients with SC. We performed gene set enrichment analysis (GSEA) to identify SC-specific gene sets. The acid-base imbalance (ABI), measured 24 h before serious complications, was higher in patients with SC than in non-SC patients. A high ABI was associated with an increased incidence of ARF, leading to mechanical ventilation and worse survival. GSEA revealed that SC correlated to gene sets reflecting inflammation/apoptotic response and airway inflammation. ABI can be used to indicate ARF in patients with SC and assist with early detection.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mike Fang ◽  
Brian Richardson ◽  
Cheryl M. Cameron ◽  
Jean-Eudes Dazard ◽  
Mark J. Cameron

Abstract Background In this study, we demonstrate that our modified Gene Set Enrichment Analysis (GSEA) method, drug perturbation GSEA (dpGSEA), can detect phenotypically relevant drug targets through a unique transcriptomic enrichment that emphasizes biological directionality of drug-derived gene sets. Results We detail our dpGSEA method and show its effectiveness in detecting specific perturbation of drugs in independent public datasets by confirming fluvastatin, paclitaxel, and rosiglitazone perturbation in gastroenteropancreatic neuroendocrine tumor cells. In drug discovery experiments, we found that dpGSEA was able to detect phenotypically relevant drug targets in previously published differentially expressed genes of CD4+T regulatory cells from immune responders and non-responders to antiviral therapy in HIV-infected individuals, such as those involved with virion replication, cell cycle dysfunction, and mitochondrial dysfunction. dpGSEA is publicly available at https://github.com/sxf296/drug_targeting. Conclusions dpGSEA is an approach that uniquely enriches on drug-defined gene sets while considering directionality of gene modulation. We recommend dpGSEA as an exploratory tool to screen for possible drug targeting molecules.


2011 ◽  
Vol 10 (4) ◽  
pp. 3856-3887 ◽  
Author(s):  
Q.Y. Ning ◽  
J.Z. Wu ◽  
N. Zang ◽  
J. Liang ◽  
Y.L. Hu ◽  
...  

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