INHBA is overexpressed in AD relative to controls. Inhibin betaA may promote cell proliferation, and its overexpression is associated with worse survival in stage I AD patients. In addition, overexpression of INHBA may be affected by promoter methylation and histone acetylation in a subset of lung ADs.

The transcription factor, nuclear factor kappaB (NF-kappaB), plays a central role as a key mediator of cell survival and proliferation, and its activation may confer increased tumor chemoresistance. Curcumin, an orally available naturally occurring compound, has been shown to inhibit NF-kappaB and has a potential role in cancer chemoprevention. We investigated the effects of curcumin on NF-kappaB activity, on cell viability, and as a chemosensitizing agent with 5-fluorouracil (5-FU) or cisplatin (CDDP) in esophageal adenocarcinoma (EAC). Oligonucleotide microarray analysis of 46 cases, consisting of Barrett metaplasia, low-grade dysplasia, high-grade dysplasia and EAC, showed increased expression of NF-kappaB and IkappaB kinase subunits and decreased effector caspase expression in EAC compared with Barrett metaplasia. Stromal expression of both IkappaB and phospho-IkappaB was detected in several EAC samples by tissue microarray analysis. Curcumin alone inhibited NF-kappaB activity and induced apoptosis in both Flo-1 and OE33 EAC cell lines as determined by Western blot analysis, NF-kappaB reporter assays, and Caspase-Glo 3/7 assays. It also increased 5-FU- and CDDP-induced apoptosis in both cell lines. These data suggest that activation of NF-kappaB and inhibition of apoptosis may play a role in the progression from Barrett metaplasia to EAC. In addition, curcumin, a well-known inhibitor of NF-kappaB activity, was shown to increase apoptosis and enhance both 5-FU- and CDDP-mediated chemosensitivity, suggesting that it may have potential application in the therapy of patients with EAC.

INHBA is overexpressed in EAC relative to dysplastic and BM tissue. INHBA overexpression may promote cell proliferation and may be affected by promoter demethylation and histone acetylation in EAC cell lines.

The presence of AZGP1 serum autoantibody may be used as a prognostic marker in patients with AD. Furthermore, up-regulation of AZGP1 mRNA in AD may be affected by chromatin remodeling by means of histone acetylation.