title: Altered gene expression in conjunctival squamous cell carcinoma.
abstract: Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Alka
authors.initials: A
authors.lastname: Mahale
authors.affiliation: Department of Ophthalmology, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hind
authors.initials: H
authors.lastname: Alkatan
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.|Department of Ophthalmology, King Saud University, Riyadh, Saudi Arabia.|Department of Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Saeed
authors.initials: S
authors.lastname: Alwadani
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Maha
authors.initials: M
authors.lastname: Othman
authors.affiliation: Department of Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Suarez
authors.affiliation: Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Price
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hailah
authors.initials: H
authors.lastname: Al-Hussain
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Sabah
authors.initials: S
authors.lastname: Jastaneiah
authors.affiliation: Microarray Core Facility, Sidney Kimmel Cancer Center, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Wayne
authors.initials: W
authors.lastname: Yu
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Azza
authors.initials: A
authors.lastname: Maktabi
authors.affiliation: King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.|Department of Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Deepak
authors.affiliation: Department of Ophthalmology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.|Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Charles G
authors.initials: CG
authors.lastname: Eberhart
authors.affiliation: Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Asnaghi
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D003230:Conjunctival Neoplasms / Q000235:genetics*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077195:Squamous Cell Carcinoma of Head and Neck; D059467:Transcriptome