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

Abstract

AimsDesmogleins (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. MethodsExpression 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. ResultsIt turned out that DSG1–3 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-aza-2′-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). ConclusionsOur 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.