Detection and analysis of differential gene expression between benign lymphoepithelial lesion of lacrimal gland and orbital cavernous hemangioma

Background

Benign lymphoepithelial lesion of lacrimal gland is not a common orbital disease in clinic, which mainly presented as symmetrical and painless enlargement of bilateral lacrimal glands.However, the etiology and pathogenesis of this disease is still unclear now.

Objective

This study was to screen the differentially expressed genes between benign lymphoid epithelial lesion of lacrimal gland and orbital cavernous hemangioma and explore the pathogenesis of benign lymphoepithelial lesion of lacrimal gland at the molecular level.

Methods

Nine patients diagnosed as benign lymphoepithelial lesion of lacrimal gland in Beijing Tongren Hospital, Capital Medical University were enrolled from September 2010 to April 2013, and nine patients with orbital cavernous hemangioma served as control group.The intraorbital tissue was collected during surgery.Whole-genome gene expression microarray was used to detect the expressed genes, and limma algorithm was used to analyze the differentially expressed genes between the benign lymphoepithelial lesion of lacrimal gland and the orbital cavernous hemangioma.Real-time PCR was used to verify differentially expressed genes, Fisher method and gene ontology (GO) functional analysis were performed to realize function and signaling pathways analysis.This study complied with Helsinki Declaration and the protocol was aproved by Institutional Review Board of Beijing Tongren Hospital, and informed consent was obtained.

Results

Total 5 260 differentially expressed genes were screened between benign lymphoepithelial lesion of lacrimal gland and orbital cavernous hemangioma.The Fisher function and signaling pathways analysis showed that 109 GO terms were significantly upregulated and 101 GO terms were significantly downregulated, and 32 relevant signaling pathways were significantly upregulated and 25 signaling pathways were significantly downregulated in the benign lymphoepithelial lesion of lacrimal gland.GO analysis showed that the expression enrichment of complement receptor-mediated signaling pathway was high, then following the upregulation of T cell and B cell signaling pathways and downregulation of mitogen-activated protein kinase (MAPK) and transforming growth factor-β (TGF-β) signaling pathways.Real-time PCR results showed that the expressions of TIPRL, TLR7 and TLR10 genes were significantly higher in the benign lymphoepithelial lesion of lacrimal gland than that in the orbital cavernous hemangioma, with significant differences between the two diseases (Z=-2.03, -2.32, -2.32; all at P<0.05), which was consistent with the microarray data.

Conclusions

Gene expression profiles are significantly different between benign lymphoepithelial lesion of lacrimal gland and orbital cavernous hemangioma.Those differentially expressed genes play roles in the upregulation of T cell and B cell signaling pathways, downregulation of MAPK and TGF-β signaling pathways and the change of complement system.It is implied that a comprehensive effect of various genes and pathways participates in the pathogenesis of benign lymphoepithelial lesion of lacrimal gland.