Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Primary Sjogren's syndrome study

ABSTRACT: The objective of the study was to identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS). METHODS: A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase-polymerase chain reaction techniques. RESULTS: We found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up-regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in >/=90% of primary SS patients and in

ORGANISM(S): Homo sapiens

SUBMITTER: Kjell Petersen

PROVIDER: E-MTAB-2073 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects.

Hjelmervik Trond Ove R TO Petersen Kjell K Jonassen Inge I Jonsson Roland R Bolstad Anne Isine AI

Arthritis and rheumatism 20050501 5

<h4>Objective</h4>To identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS).<h4>Methods</h4>A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. ...[more]

PMID: 15880807

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Project description:Primary Sjögren’s syndrome (SS or autoimmune epithelitis) is a relatively common autoimmune disorder that is primarily characterized by chronic lymphoepithelial inflammatory reactions in the exocrine glands, mainly the salivary and lachrymal glands. It may extend from disease confined to the exocrine glands (organ-specific exocrinopathy) to various extraglandular manifestations (systemic disease) and the development of B-cell lymphoma. Several studies from our laboratory had provided evidence for the strong implication of ductal salivary gland epithelial cells (SGEC) in the pathogenesis of Sjögren’s syndrome (SS), including the development of salivary gland infiltrating lesions and of adverse systemic clinical complications, such as the development of B-cell lymphoma. In fact, the comparative assessment of non-neoplastic SGEC lines derived from SS patients and disease controls had indicated that the ductal epithelia of SS patients manifest an “intrinsically activated” status that is associated with distinct aberrant phenotypic and functional features encountered in “inflamed” cells. Herein, using microarray analysis, we sought to comparatively analyze the constitutive gene expression in long-term cultured non-neoplastic SGEC lines derived from non-SS sicca control individuals and from SS patients. The study aimed to reveal the genes that are differentially expressed between SGEC lines derived from SS patients and controls, as well as between SGEC lines derived from SS patients with moderate lymphocytic infiltrations (focus score<2; SS-Group-1) and SS patients with severe lymphocytic infiltrations (focus score ≥2; SS-Group-2). The transcriptome profiling analysis presented herein lends further support to the intrinsic activation status of patients’ ductal epithelia and its association with distinct proinflammatory and metabolism-related gene signatures, which occur primarily among patients with heavy tissue infiltrates and high risk for lymphoma development.

Project description:It has been recognised for a long time that cell surface glycans plays a vital role in the biological process and their altered form can lead to cancer. However, the molecular details and regulatory mechanism between the glycans and cancer is yet not clear. Over the past decade mass spectrometry-based techniques has become a prominent method for analysing glycans especially N-glycan matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI MSI). It is a powerful technique that combines mass spectrometry with histology, enabling the visualisation and label free detection of N-linked glycans on a single tissue section. Here, we carried out N-glycan MALDI MSI on six endometrial cancer (EC) formalin fixed paraffin embedded (FFPE) tissue sections including the adjacent normal endometrium, and tissue microarrays (TMA) consisting of 8 EC patients with lymph node metastasis (LNM) and 20 without LNM. By doing that several m/z values were detected that can significantly distinguish normal endometrium from cancerous. Also, detected a m/z value that can discriminate the primary tumour with LNM from those without. Identification of those discriminative m/z values was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS). Overall, we observed higher abundance of oligomannose in tumour regions compared to normal with AUC ranges from 0.85-0.99. Whereas, complex N-glycans were detected in lower abundance with AUC ranges from 0.03-0.28. Comparison of N-glycans between the primary tumours with LNM and without LNM indicates reduced abundance of a complex core-fucosylated N-glycan in patients with metastasis relative to without. In summary, N-glycan MALDI MSI can be used to characterize the cancerous endometrium from the normal, also patients with LNM from those without. Identification of those discriminative m/z values was performed using porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS).

Dataset Information

Primary Sjogren's syndrome study

Publications

Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects.

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