Identification of Whole Blood Gene Expression Signature in Primary Sjögren’s Syndrome Associated Lymphoma

Shereen Al-Ali^1,2, Simon Cockell³, Andrew Skelton⁴, Katherine James¹, Jessica Tarn¹, David Young⁵, Bridget Griffiths⁶, Simon Bowman⁷, James Locke¹ and Wan-Fai Ng⁸, ¹Newcastle University, Newcastle upon Tyne, United Kingdom, ²College of Science, University of Basrah, Basrah, Iraq, ³Bioinformatics Support Unit, Newcastle University, Newcastle upon Tyne, United Kingdom, ⁴Bioinformatics support unit, Newcastle University, Newcastle Upon Tyne, United Kingdom, ⁵Institute of Cellular Medicine, Newcastle University, Newcastle Upon Tyne, United Kingdom, ⁶Rheumatology, Freeman Hospital, Newcastle Upon Tyne, United Kingdom, ⁷Rheumatology Dept (Selly Oak), University Hospital Birmingham, Birmingham, United Kingdom, ⁸Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Gene Expression and Sjӧgrens

Session Information

Title: Sjogren's Syndrome II: Insights into Pathophysiology

Session Type: Abstract Submissions (ACR)

Background/Purpose: Primary Sjӧgren’s syndrome (pSS) is associated with a substantially increased risk of lymphoma development. The aim of our study is to identify a whole blood gene expression signature of pSS-associated lymphoma and to explore the potential biological significance of such signature using pathway and network analysis.

Methods: Whole blood RNA samples (n =144) from pSS patients and healthy controls taken part in the UK primary Sjӧgren’s syndrome registry (UKPSSR). All patients fulfilled the AECG criteria and were stratified into five clinical subsets (pSS = 61, pSS with lymphoma = 16, pSS with other cancers=21, pSS with paraproteinemia = 23 and healthy controls = 23). RNA was extracted and globin mRNA were removed using GLOBINClear kit. Whole genome microarray (illumina, HumanHT-12 v4 BeadChips) was used for gene expression profiling. Microarray data were analyzed by R Bioconductor. The differentially expressed genes between the pSS-associated lymphoma group and pSS patients without lymphoma were validated using RT-PCR.

Results: Distinct gene expression profiles and similar differentially expressed genes were observed when comparing each clinical subset with healthy controls. Comparison between the “Lymphoma” group and those without lymphoma revealed 25 upregulated genes and 43 downregulated genes. When compared with pSS patients with other cancers, only one gene was differentially expressed and it was downregulated in the “lymphoma” group. No differentially expressed gene were found when comparisons were made between other clinical subsets. Go terms and KEGG pathway analysis revealed 14 biological processes and 23 different biological pathways that might be important which included (e.g. mismatch Repair , T-cell receptor signaling pathway and pathways in cancer)

Conclusion: A potential gene expression signature for pSS-associated lymphoma was identified. Further experiments to validate the biosignature with another cohort and to evaluate the sensitivity and specificity of such signature are in progress.

Disclosure:

S. Al-Ali,
None;

S. Cockell,
None;

A. Skelton,
None;

K. James,
None;

J. Tarn,
None;

D. Young,
None;

B. Griffiths,
None;

S. Bowman,
None;

J. Locke,
None;

W. F. Ng,
None.

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