Expression of desmogleins 1-3 and their clinical impacts on human lung cancer

Aims: Desmogleins (DSGs) are components of the cell-cell connecting desmosomes. Desmosomal proteins have been found dysregulated in various cancers. Here we studied the role of DSGs in human lung cancer. Methods: Expression of DSG1-3 mRNA in lung cancer cell lines and human bronchial epithelial cells (HBEC) was examined by real time RT-PCR. Methylation status of DSG1-2 was evaluated by demethylation test and bisulfite sequencing (BS). Moreover, DSG1-3 protein expression was analysed in 112 primary lung tumor samples by immunohistochemistry (IHC) on tissue microarrays. Results: It turned out that DSGI-3 was downregulated in most of the lung cancer cell lines. Reexpression of DSG2 and DSG3 was found in several cancer cell lines after demethylation treatment with 5-aza2'-deoxycytidine (DAC), a DNA methyltransferase inhibitor. Complete or partial methylation of DSG2 promoter region was detected in 5 out of 6 cancer cell lines by BS. In primary lung tumors, higher protein expression of DSG2 and DSG3 correlated to the diagnosis of squamous cell lung carcinoma (SCC)(P = 0.009 and P<0.001, respectively), additionally, a lower expression of DSG3 was significantly linked to higher tumor grade (P=0.012). Conclusions: Our data suggest that downregulation of DSG2 and DSG3 could be partially explained by DNA methylation. DSG2 and DSG3 might be potential diagnostic markers for SCC, and DSG3 could be a potential differentiation marker for lung cancer. (C) 2014 Elsevier GmbH. All rights reserved.