The Role Of NF-kB And PPAR-γ In The Development Of Barrett's Esophagus And Esophageal Adenocarcinoma

Background: Esophageal adenocarcinoma(EA) may arise in a backgroud of Barrett's Esophagus (BE). There has been a marked increase in the incidence of esophageal adenocarcinoma over the last 2 decades. NF-κB and PPAR-γhave association with inflammatory and apoptotic responses, but their roles in Barrett's esophagus and Esophageal Adenocarcinoma have not been reported.Objective: To explore the pathogenesis and discover the role of NF-κB and PPAR-γin the development of BE and EA.Methods: The expressions of protein and mRNA of NF-κB and PPAR-γwere investigated in normal esophageal squamous epithelium(n=75), BE(n=50) and EA(n=25) using immunohistochemical staining and real-time PCR respectively. The differences among the three groups were compared and the correlations were analyzed .Result: The protein expression level of NF-κB was few in normal esophageal squamous epithelium,but was more in BE and EA.There was a statistically significance in NF-κB staining(P<0.01) among these three groups.Moreover, an increasing intendency was observed from normal esophageal squamous epithelium to BE and EA(P<0.01).Positive staining lied in cytoplasm of goblet cell and surface glandular epithelium in BE. NF-κB mRNA and PPAR-γmRNA was detected in these three groups by real-time PCR.The expressing of NF-κB mRNA and PPAR-γmRNA in BE was 1.2058 times(P<0.01) and 5.9130 times(P<0.01) of normal esophageal squamous epithelium,respectively.Similarly, the expressing of NF-κB mRNA and PPAR-γmRNA in EA was 1.7212 times(P<0.01) and 2.0314 times(P<0.01) of normal esophageal squamous epithelium,respectively. The level of PPAR-γprotein expression was low in normal esophageal squamous epithelium,in contrast to high expression in BE and EA(P<0.01).Moreover,we also observed an increasing tendency in these three groups(P<0.01).Positive staining region was as same as NF-κB staining.The median age of these EA patients is 61.5 years old.The median length of EA is 5cm.Comparately, tubular adenocarcinoma, papillary adenocarcinoma, and adenosquamous carcinoma was common, mucinous adenocarcinoma and signet-ring cell carcinoma was rare. StageⅡor stageⅢand lymph node metastasis was common when these patients were diagnosised.There was significant correlation between the expression of NF-κB and cell difference or pathologic stage in EA(P<0.05).Similary, there was a correlation between the expression of PPAR-γand EA cell difference(P<0.05).Conclusion: The up-regulation of NF-κB and PPAR-γin BE and EA may play an important role in the development of neoplastic progression.