Gene Expression Profiling of Idiopathic Orbital Inflammatory Pseudotumors

Propose: Idiopathic orbital inflammatory pseudotumors (IOIP) are inflammatory pseudotumors (IPT) of unknown etiology that develop in the orbit. Due to the lack of well-defined pathogenic mechanisms and diagnostic markers, diagnosis and treatment of this disease remain a significant challenge. Therefore, the aims of this study are to define the etiological factors of IOIP and to identify potential gene targets for the treatment of IOIP. Methods: Eleven IOIP tissue samples were obtained from patients during surgical resection; as control tissue, four normal tissue samples were collected from surgery removal of eye due to trauma. Total RNA was extracted and the gene expression profile of both diseased and normal tissues was analyzed using human oligonucleotide microarrays, which contained 32,050 well-characterized human genes. The expression patterns of selected genes were further confirmed by Real-time RT-PCR. Results: Microarray analyses identified 744 genes differentially expressed in IOIP and non-IOIP samples, with at least 2^1.5-fold changes and P-value <; .005, including 552 downregulated and 192 upregulated genes in IOIPs. Principal Component Analysis (PCA) and Hierarchical Clustering of microarray data successfully distinguished the IOIP group from the non-IOIP control group. Functional annotation using the Molecule Annotation System categorized the 744 genes into immune functions, inflammatory responses, signaling molecules in the PI3K and NF-κB pathways, extracellular matrix degradation, and unknown functions. Conclusions: Immune and inflammatory responses and activation of the PI3K and NF-κB pathways are likely associated with IOIPs. Drugs that would suppress these two responses and two signal pathways may offer new therapeutics of IOIP treatment.