Abstract
BackgroundThe incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised.MethodsIn this study, we used a comparative proteomic approach to analyse the malignant and nonmalignant gastric cardia epithelial cells isolated by navigated laser capture microdissection (LCM) from paired surgical specimens of human GCA.ResultsTwenty-seven spots corresponding to 23 proteins were consistently differentially regulated. Fifteen proteins were shown to be up-regulated, while eight proteins were shown to be down-regulated in malignant cells compared with nonmalignant columnar epithelial cells. The identified proteins appeared to be involved in metabolism, chaperone, antioxidation, signal transduction, apoptosis, cell proliferation, and differentiation. In addition, expressions of HSP27, 60, and Prx-2 in GCA specimens were further confirmed by immunohistochemical and western blot analyses.ConclusionThese data indicate that the combination of navigated LCM with 2-DE provides an effective strategy for discovering proteins that are differentially expressed in GCA. Such proteins may contribute in elucidating the molecular mechanisms of GCA carcinogenesis. Furthermore, the combination provides potential clinical biomarkers that aid in early detection and provide potential therapeutic targets.
Highlights
The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised
This study aims to outline the carcinogenesis of GCA and to identify GCA-specific disease-associated proteins as potential clinical biomarkers for early detection and new therapeutic targets
This phenomenon is likely due to post-translational modifications like peroxiredoxin 1 (Prx-1), which was present in two adjacent spots (Fig. 2, spot 11)
Summary
The incidence of gastric cardiac adenocarcinoma (GCA) has been increasing in the past two decades in China, but the molecular changes relating to carcinogenesis have not been well characterised. Various analyses of cancer incidence data culled from Western countries have revealed rapidly rising rates of adenocarcinoma of the esophagus and gastric cardia in the last few decades, compared with the stable and declining rates for esophageal squamous cell carcinoma (SCC) and distal gastric adenocarcinoma (DGA) [1-3]. This phenomenon is apparent in China, except that the increasing incidence of gastric cardia adenocarcinoma (GCA) appears notably higher than the incidence of esophageal cancer.
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