canonical pathway analysis
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e19563 Background: Bidirectional relationship between non-Hodgkin’s lymphoma (NHL) and Sjögren’s syndrome (SS) has been recognized in large-scale cohort studies. We identified significant differentially expressed genes for SS-associated NHLs, and evaluated whether these genes could serve as a prognostic biomarker of diffuse large B-cell lymphoma (DLBCL). Methods: RNA-sequencing data from whole-transcriptome expression profiling were compared in a canonical pathway analysis using z-score and p-value visualization to identify significant differentially expressed genes and underlying cellular mechanisms for SS-associated NHLs including Burkitt lymphoma (BL), DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Collected biopsies included lymphoma biopsies for BL (n = 59), DLBCL (n = 88), FL (n = 65), MCL (n = 43), and MZL (n = 23), sorted B cells from healthy donors (n = 10), as well as parotid gland tissues for SS (n = 17). RNA-seq data with P values less than 0.05 or -log10(P) larger than 1.3 were considered significant, and positive z-scores indicated up-regulation while negative z-scores indicated down-regulation. After screening potential biomarkers through canonical pathway analysis, significant differentially expressed genes were subjected to survival analysis with genomic and clinical data of 420 DLBCL patients from The Cancer Genome Atlas (TCGA) using a log-rank test. Area under the ROC curve (AUC) was derived to validate the predictive ability of the survival model. Results: Among all genes involved in SS-associated NHLs, 16 genes were significantly differentially expressed in all types of NHLs. These genes included CXCL13, SEPP1, COL1A1, RGS13, IGFBP7, COL3A1, SPARCL1, GABBR1, SLC40A1, CXCL14, CXCL12, CXCL9, CCL19, VCAM1, C3, and CLU. The fold changes of the 16 genes for DLBCL were 465.67, 209.68, 436.94, 366.94, 189.59, 456.09, 195.37, 152.05, 90.29, 26.29, 215.18, 72.06, 51.09, 91.91, 74.70, and 20.88, respectively. Among all SS-associated pathways underlying NHL pathogenesis, the endocannabinoid system-driven cancer inhibition pathways were most significantly altered in SS-associated NHLs. The z-scores of the cancer inhibition pathway were -0.14 for BL (-log10(P) = 4.54), -1.298 for DLBCL (-log10(P) = 3.00), -0.33 for FL (-log10(P) = 4.67), -0.87 for MCL (-log10(P) = 3.77), and -2.61 for MZL (-log10(P) = 4.31). Survival analysis revealed that together the 16 genes may serve as a prognostic biomarker of DLBCL (hazard ratio = 3.57, 95% CI = 2.53–5.03), which was statistically significant (log rank test P < 0.0001) and reliable (AUC = 0.897). Conclusions: Significant differentially expressed genes underlying the pathogenesis for SS-associated NHLs may be used as a biomarker for predicting the survival rate of DLBCL. Further studies are warranted to elucidate the functional association between these differentially expressed genes.

Background:Periodontal pathogens such as Porphyromonas gingivalis (P.g.) has been proposed too involve in rheumatoid arthritis (RA) progression via citrullinating and producing exogenously citrullinated human and bacterial epitopes.Objectives:We identified pathways downstream to periodontitis onset that involved in RA progression with RNA-sequencing data.Methods:Canonical pathway analysis was conducted by comparing mRNA expression data from whole-transcriptome expression profiling using z-score and p-value visualization to identify underlying mechanisms among patients with RA (n=7) and periodontitis (n=9). Collected biopsies included human blood samples for RA and human gingival tissues for periodontitis. RNA-seq data with -log10(P) values larger than 1.3 were considered significant, and positive z-scores indicated up-regulation. The statistical software was Ingenuity Pathway Analysis (QIAGEN).Results:Among all significantly enriched (-log10(P) > 1.3) periodontitis-associated pathways underlying RA progression identified from the recruited cases, the production of nitric oxide and reactive oxygen species in macrophages, B cell receptor signaling, osteoarthritis pathway, HOTAIR regulatory pathway, IL-8 signaling, LPS/IL-1 mediated inhibition of RXR function, leukocyte extravasation signaling, and neuroinflammation signaling pathway, were up-regulated in RA patients and patients with periodontitis, when compared with patients without either disease. The z-scores of production of nitric oxide and reactive oxygen species in macrophages were 2.45 for RA (-log10(P) = 1.41), 3.89 for periodontitis (-log10(P) = 4.25); the z-scores of B cell receptor signaling were 2.44 for RA (-log10(P) = 1.93), 2.65 for periodontitis (-log10(P) = 6.97); the z-scores of osteoarthritis pathway were 1.89 for RA (-log10(P) = 3.28), 2.33 for periodontitis (-log10(P) = 4.31); the z-scores of HOTAIR regulatory pathway were 1.63 for RA (-log10(P) = 1.71), 3.40 for periodontitis (-log10(P) = 3.68); the z-scores of IL-8 signaling were 1.34 for RA (-log10(P) = 1.30), 4.43 for periodontitis (-log10(P) = 6.05); the z-scores of LPS/IL-1 mediated inhibition of RXR function were 1.33 for RA (-log10(P) = 2.00), 1.27 for periodontitis (-log10(P) = 3.44); and the z-scores of leukocyte extravasation signaling were 1.13 for RA (-log10(P) = 1.80), 3.68 for periodontitis (-log10(P) = 18.14).Conclusion:Our findings suggest that infection-driven activation of macrophages and B cells is involved in RA pathogenesis. This occurs primarily through upregulating cellular activities involving iNOS-presenting macrophages and B cell receptor signaling, which may be associated with the pathogenesis of P.g.-triggered RA.References:[1]Jenning M, Marklein B, Ytterberg J, et al. Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production. Ann Rheum Dis 2020;79:1194–202.doi:10.1136/annrheumdis-2019-216919Figure 1.Canonical pathway analysis on transcriptome of blood samples for patients with RA and gingival tissues for periodontitis.Disclosure of Interests:None declared

Depression is a global mental disorder disease and greatly threatened human health and stress is considered to be one of the important factors that lead to depression. In this study, we used newly developed iTRAQ labeling and high performance liquid chromatography (HPLC) and mass spectrum united analysis technology obtained the 2176 accurate proteins. Successively, we used the GO analysis and IPA software to analyze the 98 differentially expressed proteins of liver in depression rats due to chronic restraint stress, showing a map of proteomics analysis of liver proteins from the aspects of related functions, disease and function analysis, canonical pathway analysis, and associated network. This study provide important information for comprehensively understanding the mechanisms of dysfunction or injury in the liver in depression.