engleski

Glyco-gene expression and methylation in cancer: a meta-analysis

Most of eukaryotic proteins are modified by covalent addition of glycan molecules, which modulates their structure and function. Such glycoproteins are important in fundamental biological processes including cell signaling, interactions and immunity. Aberrant glycosylation plays a key role in pathogenesis of many complex diseases including cancer. Furthermore, certain glycan structures are specific for tumors thus reflecting altered glycan biosynthesis through altered expression of enzymes involved in synthetic pathways. While mutations in genes coding for glycosyltransferases (i.e. glyco-genes) are rare, epigenetic deregulation is the most probable mechanism underlying their aberrant expression. A comprehensive picture of this process is emerging based on the rapidly accumulating data. First, we analyzed promoter methylation and expression status of 86 glyco- genes in melanoma, hepatocellular, breast and cervical carcinoma by performing a meta- analysis of data available in the Gene Expression Omnibus (GEO) database. We identified ten glyco-genes that change both methylation and expression in all analyzed types of tumors. Our findings are in line with changes in glycan structures previously reported in the same type of tumors. Some of those genes were additionally identified as potentially valuable for disease prognosis. The ability to identify glyco-genes with commonly changed expression/methylation in different types of cancer points to potential new targets for epigenetic drugs. In the second part of the study, we focused on the RASSF1A gene in testicular cancer (TC), a putative tumor suppressor frequently silenced by promoter methylation in different tumor types. We conducted a meta-analysis assessing the risk of TC given the RASSF1A methylation status. We found significant association between RASSF1A promoter methylation and TC risk (odds ratio 8.61). This association was stronger when samples were stratified according to TC subtype (seminoma versus non-seminoma). The results suggest early diagnostic value of the RASSF1A gene when promoter methylation analyzed from whole blood.

meta-analysis ; DNA methylation ; gene expression ; glyco-genes ; RASSF1A ; cancer

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