Differential Expression of Desmocollin2, Desmoglein2, and Plakophilin2 in the Progression of Esophagitis to Esophageal Adenocarcinoma

Abstract

BackgroundDesmosomes play a key role in intercellular adhesive, but also contribute to tumorigenesis. This study aimed to examine the differential expression of desmocollin2 (DSC2), desmoglein2 (DSG2), and plakophilin2 (PKP2) in the progression of reflux esophagitis to esophageal adenocarcinoma (EAC) in the rat model of reflux disease established by esophagogastroduodenal anastomosis (EGDA).MethodsEGDA was performed on rats to induce gastroesophageal reflux leading to the development of EAC. All rats were randomly divided into four groups: group A rats received EGDA only (n=27); group B rats received EGDA and iron supplementation (n=28); group C received pseudo surgery only (n=20); group D received pseudo surgery and iron supplementation (n=20). Animals were randomly selected from each group and euthanized at 8 weeks and 32 weeks following EGDA. Esophageal tissues were harvested and divided into 4 types (normal esophagus, esophagitis, dysplasia, and EAC). On these tissue types, immunohistochemistry was performed to characterize the localization and distribution of DSC2, DSG2, and PKP2, while qRT-PCR and western blot were performed to detect the expression of DSC2, DSG2, and PKP2 at the gene and protein levels.ResultsAt 8 weeks after surgery, 80% of rats in group A and 100% in group B had esophagitis. At 32 weeks, 29.41% and 17.65% of rats in group A developed dysplasia and EAC, respectively, while in group B, dysplasia and EAC accounted for 44.44% and 38.89%, respectively. The expression of DSC2, DSG2, and PKP2 at both the gene and protein levels increased progressively from esophagitis to dysplasia, and EAC. Of note, all of the three genes were significantly upregulated in EAC tissues compared with tissues of esophagitis.ConclusionDSC2, DSG2, and PKP2 may play an important role in the progression of esophagitis to EAC. Their expression levels may therefore be utilized as molecular biomarkers for early diagnosis and targeted therapy for EAC.