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| Title / Description | Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures |
| Accession | GSE68698 |
| Summary | Esophageal involvement in patients with systemic sclerosis (SSc) is common, but tissue-specific pathological mechanisms are poorly understood. Fibrosis in the esophagus is thought to disrupt smooth muscle function and lead to esophageal dilatation, but autopsy studies demonstrate esophageal smooth muscle atrophy and the absence of fibrosis in the majority of SSc cases. Molecular characterization of SSc esophageal pathology is lacking. Herein, we perform a detailed characterization of SSc esophageal histopathology and molecular signatures at the level of gene expression. Esophageal biopsies were prospectively obtained during esophagogastroduodenoscopy in 16 consecutive SSc patients and 7 subjects without SSc. Upper and lower esophageal biopsies were evaluated for histopathology and gene expression. Individual patient’s upper and lower esophageal biopsies showed nearly identical patterns of gene expression. Similar to skin, inflammatory and proliferative gene expression signatures were identified suggesting that molecular subsets are a universal feature of SSc end-target organ pathology. The inflammatory signature was present in biopsies without high numbers of infiltrating lymphocytes. Molecular classification of esophageal biopsies was independent of SSc skin subtype, serum autoantibodies and esophagitis. Proliferative and inflammatory molecular gene expression subsets in tissues from patients with SSc may be a conserved, reproducible component of SSc pathogenesis. The inflammatory signature is observed in biopsies that lack large inflammatory infiltrates suggesting that immune activation is a major driver of SSc esophageal pathogenesis. |
| Organism | Homo sapiens |
| Platform | GPL6480 |
| Normalized | False |
| Parsed SOFT file |
| Differential expression method | Characteristic Direction |
| Cutoff | 500 |
| Cell | Esophageal tissue |
| Disease | Relevant info: Gene expression analysis of control upper & lower esophageal tissue vs SSc upper & lower esophageal tissue |
| Principal Component Analysis | |
| Hierarchical clustering |
| Gene lists | Enrichr | L1000CDS2 | PAEA | |
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