Diagnostic and prognostic impact of desmocollins in human lung cancer

Abstract

Objective Desmosomes are intercellular junctions that confer strong cell-cell adhesion. Two main members of desmosomal cadherins, desmogleins (DSGs) and desmocollins (DSCs), are involved in carcinogenesis. However, their role in human lung cancer remained elusive. The aims of this study were to analyse the expression of DSCs and to evaluate their clinical application in lung cancer. Methods The expression of DSC1-3 mRNAs was analysed by RT-PCR. The methylation status of DSCs was analysed by demethylation tests and bisulphite sequencing. Protein expression of DSCs in primary lung cancer was evaluated by immunohistochemistry on tissue microarrays. Results DSC1-3 mRNAs were downregulated in lung cancer cells, and the expression was restored in four out of seven cell lines, respectively, after 5-aza-2 0 -deoxycytidine treatment. A heterogeneous methylation pattern was detected by bisulphite sequencing in exon 1 of DSC2 and DSC3. In 199 patients with primary lung cancer, we found that lower protein expression of DSC1 was significantly linked to worse tumour differentiation (p=0.017), DSC3 proteins were more expressed in squamous cell carcinoma (SCC) compared with adenocarcinoma (ADC) ( p<0.001), and reduced expression of DSC1 and DSC3 was significantly correlated with poor clinical outcome ( p=0.045 and p=0.007, respectively). Conclusions Our data suggest that downregulation of DSC1-3 may be explained by DNA methylation, DSC1 may be a marker for tumour differentiation, DSC3 has a potential diagnostic value in subclassification of non-small cell lung carcinoma into SCC and ADC, and furthermore, DSC1 and DSC3 may be prognostic markers for lung cancer.

Desmocollin-3 and Cancer

“…Sensitivity of DSC3 for squamous NSCLC is 93.2% in large cohort of 426 but drops to 59% in poorly differentiated squamous NSCLC (Table 1). DSC3 expression in NSCLC is also not related to stage or histologic grade [17] of a disease [46].…”

“…Immunohistochemistry reveals in lung cancer expression of DSC3 is seen at basal layers of tumor. DSC3 expression is seen in around 30% of cases [17]. DSC 3 expression is seen in squamous NSCLC and not in adenocarcinoma of lung.…”

Desmosomes in acquired disease

“…Slug has also been implicated in FGF-1-induced alterations in border localization of Dsg1/2 and desmoplakin in NBT-II bladder carcinoma cells (Savagner, et al, 1997, Thiery and Chopin, 1999). DNA methylation also plays a role in the reduced expression of Dsc1, Dsc2, Dsc3 and desmoplakin in lung cancer (Cui, et al, 2012a, Cui, et al, 2012b). Furthermore, the protease kallikrein has been linked to the reduced expression of Dsg1 and Dsg2 in pancreatic adenocarcinoma (Ramani, et al, 2008).…”

The role of Napsin-A and Desmocollin-3 in classifying poorly differentiating non-small cell lung carcinoma

“…They noticed that DSC1-3 mRNAs were down regulated in lung cancer cells. In a study that included 199 patients with a history of primary lung cancer, they found that DSC3 proteins were more expressed in SCC compared with ADC (p < 0.001), and that reduced expression of DSC3 was correlated with poor clinical outcome [32].…”