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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2019

Open Access 01-12-2019 | Research article

Integrated systems analysis of salivary gland transcriptomics reveals key molecular networks in Sjögren’s syndrome

Authors: Hong Ki Min, Su-Jin Moon, Kyung-Su Park, Ki-Jo Kim

Published in: Arthritis Research & Therapy | Issue 1/2019

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Abstract

Background

Treatment of patients with Sjögren’s syndrome (SjS) is a clinical challenge with high unmet needs. Gene expression profiling and integrative network-based approaches to complex disease can offer an insight on molecular characteristics in the context of clinical setting.

Methods

An integrated dataset was created from salivary gland samples of 30 SjS patients. Pathway-driven enrichment profiles made by gene set enrichment analysis were categorized using hierarchical clustering. Differentially expressed genes (DEGs) were subjected to functional network analysis, where the elements of the core subnetwork were used for key driver analysis.

Results

We identified 310 upregulated DEGs, including nine known genetic risk factors and two potential biomarkers. The core subnetwork was enriched with the processes associated with B cell hyperactivity. Pathway-based subgrouping revealed two clusters with distinct molecular signatures for the relevant pathways and cell subsets. Cluster 2, with low-grade inflammation, showed a better response to rituximab therapy than cluster 1, with high-grade inflammation. Fourteen key driver genes appeared to be essential signaling mediators downstream of the B cell receptor (BCR) signaling pathway and to have a positive relationship with histopathology scores.

Conclusion

Integrative network-based approaches provide deep insights into the modules and pathways causally related to SjS and allow identification of key targets for disease. Intervention adjusted to the molecular traits of the disease would allow the achievement of better outcomes, and the BCR signaling pathway and its leading players are promising therapeutic targets.
Appendix
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Metadata
Title
Integrated systems analysis of salivary gland transcriptomics reveals key molecular networks in Sjögren’s syndrome
Authors
Hong Ki Min
Su-Jin Moon
Kyung-Su Park
Ki-Jo Kim
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2019
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-019-2082-9

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