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Altered gene expression in conjunctival squamous cell carcinoma

机译：结膜鳞状细胞癌中基因表达的改变

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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.
机译：结膜鳞状细胞癌是眼表的恶性肿瘤。导致这种疾病发生和发展的分子驱动因素尚未广为人知。因此，我们比较了八种速冻结膜鳞状细胞癌和一种原位病变与正常结膜标本的转录谱，以鉴定诊断标记或治疗靶标。使用寡核苷酸微阵列分析了RNA，并鉴定了表达变化的多种转录物，包括许多在其他位点发生的癌基因失调。在上调的基因中，我们观察到基质金属蛋白酶MMP-9和MMP-11的诱导超过30倍，并且钙结合蛋白的mRNA水平显着增加，这对于细胞内钙信号传导S100A2很重要，在肿瘤队列中被诱导超过20倍。簇蛋白是最下调的基因，其mRNA表达降低约180倍。通过qPCR在用于初始微阵列分析的样品中均确认了这些改变。此外，免疫组织化学分析证实了几种独立的结膜原位癌中MMP-11和S100A2的过度表达以及簇蛋白的减少。这些数据确定了许多变化，包括MMP-9，MMP-11和S100A2的上调，以及簇蛋白的下调，这些变化与眼表皮上皮的肿瘤发生有关。

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