RESEARCH - Systems biology analysis of Sjogren's syndrome and mucosa-associated lymphoid tissue lymphoma in parotid glands

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Arthritis Rheum. 2009 Jan;60(1):81-92.

Systems biology analysis of Sjögren's syndrome and mucosa-associated

lymphoid tissue lymphoma in parotid glands.

Hu S, Zhou M, Jiang J, Wang J, Elashoff D, Gorr S, Michie SA,

Spijkervet FK, Bootsma H, Kallenberg CG, Vissink A, Horvath S, Wong

DT.

University of California, School of Dentistry, Los Angeles, CA 90095-1668, USA.

OBJECTIVE: To identify key target genes and activated signaling

pathways associated with the pathogenesis of Sjögren's syndrome (SS)

by conducting a systems analysis of parotid glands manifesting primary

SS or primary SS/mucosa-associated lymphoid tissue (MALT) lymphoma

phenotypes.

METHODS: A systems biology approach was used to analyze parotid gland

tissue samples obtained from patients with primary SS, patients with

primary SS/MALT lymphoma, and subjects without primary SS (non-primary

SS controls). The tissue samples were assessed concurrently by

gene-expression microarray profiling and proteomics analysis, followed

by weighted gene-coexpression network analysis.

RESULTS: Gene-coexpression modules related to primary SS and primary

SS/MALT lymphoma were significantly enriched with genes known to be

involved in the immune/defense response, apoptosis, cell signaling,

gene regulation, and oxidative stress. Detailed functional pathway

analyses indicated that primary SS-associated modules were enriched

with genes involved in proteasome degradation, apoptosis, signal

peptides of the class I major histocompatibility complex (MHC),

complement activation, cell growth and death, and integrin-mediated

cell adhesion, while primary SS/MALT lymphoma-associated modules were

enriched with genes involved in translation, ribosome biogenesis and

assembly, proteasome degradation, class I MHC signal peptides, the G13

signaling pathway, complement activation, and integrin-mediated cell

adhesion. Combined analyses of gene expression and proteomics data

implicated 6 highly connected " hub " genes for distinguishing primary

SS from non-primary SS, and 8 hub genes for distinguishing primary

SS/MALT lymphoma from primary SS.

CONCLUSION: Systems biology analyses of the parotid glands from

patients with primary SS and those with primary SS/MALT lymphoma

revealed pathways and molecular targets associated with disease

pathogenesis. The identified gene modules/pathways provide further

insights into the molecular mechanisms of primary SS and primary

SS/MALT lymphoma. The identified disease-hub genes represent promising

targets for therapeutic intervention, diagnosis, and prognosis.

PMID: 19116902

http://www.ncbi.nlm.nih.gov/pubmed/19116902

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