Dataset Information

Identification of pathways significantly associated with spondyloarthropathy/ankylosing spondylitis using the sub?pathway method.

ABSTRACT: The aim of the present study was to extract potential sub?pathway biomarkers for spondyloarthropathy (SpA)/ankylosing spondylitis (AS) using a sub?pathway strategy. SpA/AS?relevant data, reference pathways and long non?coding (lnc)RNA?micro (mi)RNA?mRNA interactions were downloaded. The seed pathways based on Kyoto Encyclopedia of Genes and Genomes pathways and the mRNAs in the co?expressed lncRNA?mRNA interactions were extracted. Sub?pathways regulated by lncRNA were selected after establishing condition?specific lncRNA competitively regulated pathways (LCRP) network. Significant sub?pathways were further identified using the attract method. These significant sub?pathways were evaluated in the other independent published AS microarray data (E?GEOD?25101) using in silico validation. In addition, to uncover SpA/AS?relevant lncRNAs, the degree analysis for all nodes in the LCRP network was conducted. A total of 35 lncRNAs, 131 mRNAs and 145 co?expressed interactions were identified. When entering these 131 mRNAs into the reference pathways, 82 seed pathways were extracted, which were transformed into undirected graphs, and the 35 lncRNAs were mapped to the pathway graphs to further establish the condition?specific LCRP network. Based on degree analysis, four hub lncRNAs were selected, including C14orf169, LINC00242, LINC00116 and LINC00482. It was identified that 35 lncRNAs competitively regulating sub?pathways were involved in 56 complete pathways. Among these, the top three sub?pathways were path: 04010_1, which was a subregion of the mitogen?activated protein kinase (MAPK) signaling pathway; path: 04062?1, an important subregion in the chemokine signaling pathway; and path: 04066_2, was a part of HIF?1 signaling pathway. Furthermore, it was validated consistently in the separate microarray data set E?GEOD?25101. Cancer?associated pathways and hub node C14orf169 were identified in validation. Sub?pathways, including the MAPK signaling pathway and chemokine signaling pathway, and hub lncRNA (C14orf169) may serve important roles in SpA/AS.

SUBMITTER: Ding M

PROVIDER: S-EPMC6131564 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Identification of pathways significantly associated with spondyloarthropathy/ankylosing spondylitis using the sub‑pathway method.

Ding Ming M Guan Ting-Jin TJ Wei Chuan-Yin CY Chen Bo-Hua BH

Molecular medicine reports 20180817 4

The aim of the present study was to extract potential sub‑pathway biomarkers for spondyloarthropathy (SpA)/ankylosing spondylitis (AS) using a sub‑pathway strategy. SpA/AS‑relevant data, reference pathways and long non‑coding (lnc)RNA‑micro (mi)RNA‑mRNA interactions were downloaded. The seed pathways based on Kyoto Encyclopedia of Genes and Genomes pathways and the mRNAs in the co‑expressed lncRNA‑mRNA interactions were extracted. Sub‑pathways regulated by lncRNA were selected after establishing ...[more]

PMID: 30132545

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Project description:We have compared synovial biopsies from ankylosing spondylitis and undifferentiated spondylitis patients with healthy controls and osteoarthritis patients Objective: In spondylarthropies, whole-genome gene expression profiling studies have been limited to peripheral blood to date. By undertaking a study in knee synovial biopsies from spondylarthropy (SpA) and ankylosing spondylitis (AS) patients we aimed to identified joint-specific candidate genes and pathways. These pathways may mediate systemic inflammation driven joint damaging processes and more specifically, the osteoproliferation that is characteristic of these conditions. Methods: RNA was extracted from six seronegative SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: 416 differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, osteoblast activity, B-cell associated, matrix catabolic, and metabolic pathways. The inflammatory mediator, MMP3, was strongly upregulated in AS/SpA samples and the Wnt pathway inhibitors DKK3 and Kremen1 were downregulated. Conclusion: Pathways mediating both systemic inflammation as well as local tissue changes were identified. This suggests initial systemic inflammation in spondylarthropies transfers to and persists in the local joint environment, subsequently mediating changes in genes directly involved in the destructive tissue remodelling. Fifteen knee synovial biopsy tissue samples consisting of six seronegative spondyloarthropy (SpA), two ankylosing spondylitis (AS), three osteoarthritis (OA) and four normal control biopsies were obtained from the Synovial Tissue Bank at the Repatriation General Hospital in Adelaide, South Australia with the appropriate ethical approval (Supplementary Table 1). All patients provided informed written consent.

Dataset Information

Identification of pathways significantly associated with spondyloarthropathy/ankylosing spondylitis using the sub?pathway method.

Publications

Identification of pathways significantly associated with spondyloarthropathy/ankylosing spondylitis using the sub‑pathway method.

Similar Datasets

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