MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma

John C Bladen,Claude Chelala,Mariya Moosajee,Jun Wang,Daniel G Ezra,Edel A O’Toole,Ajanthah Sangaralingam,Michele Beaconsfield,Caroline Fitchett,Michael P Philpott

doi:10.1038/s41598-018-25900-z

Abstract

Sebaceous gland carcinoma (SGC) is a rare, but life-threatening condition with a predilection for the periocular region. Eyelid SGC can be broadly categorised into two subtypes, namely either nodular or pagetoid with the latter being more aggressive and requiring radical excision to save life. We have identified key altered microRNAs (miRNA) involved in SGC shared by both subtypes, hsa-miR-34a-5p and hsa-miR-16-5p. However, their gene targets BCL2 and MYC were differentially expressed with both overexpressed in pagetoid but unchanged in nodular suggesting different modes of action of these two miRNAs on BCL/MYC expression. Hsa-miR-150p is nodular-specifically overexpressed, and its target ZEB1 was significantly downregulated in nodular SGC suggesting a tumour suppressor role. Invasive pagetoid subtype demonstrated specific overexpression of hsa-miR-205 and downregulation of hsa-miR-199a. Correspondingly, miRNA gene targets, EZH2 (by hsa-miR-205) and CD44 (by hsa-miR-199a), were both overexpressed in pagetoid SGC. CD44 has been identified as a potential cancer stem cell marker in head and neck squamous cell carcinoma and its overexpression in pagetoid cells represents a novel treatment target. Aberrant miRNAs and their gene targets have been identified in both SGC subtypes, paving the way for better molecular understanding of these tumours and identifying new treatment targets.

Highlights

Sebaceous gland carcinoma (SGC) is a rare, aggressive cancer that has a predilection for the periorbital region, perhaps due to the multitude of glands surrounding the globe, but can come from extraocular sites, albeit mainly within the head region[1]
Thirty-nine differentially expressed (DE) miRNA were common to both subtypes with the majority being upregulated (Fig. 1A)
As MYC is over-expressed in the pagetoid subtype, our results suggest that hsa-miR34a may play a tumour activating and enhancing role, but not the case in nodular SGC where the expression of MYC was unchanged compared to normal control (Fig. 1D)

Summary

Introduction

Sebaceous gland carcinoma (SGC) is a rare, aggressive cancer that has a predilection for the periorbital region, perhaps due to the multitude of glands surrounding the globe, but can come from extraocular sites, albeit mainly within the head region[1]. -518d downregulated), these miRNAs were compared to sebaceous adenoma rather than normal tissue and no histological subtype analysis was made[12]. SGC prognosis is dependent on the subtype, with pagetoid conferring a poorer prognosis and nodular a better prognosis[8]. In this study we assess periocular SGC whole-miRNA profile normalised to eyelid tarsal plate, the presumed tissue of origin. We have identified aberrantly expressed miRNAs unique to pagetoid and nodular SGC along with shared aberrant miRNAs. Subsequently, a combination of in-silico miRNA target search and transcriptome profiling, as well as miRNA-target gene network analysis, was performed to highlight miRNA targets in both subtypes

Methods

Results

Conclusion