S1953 Biomarkers Predicting Future Development of Gastric Cancer in Japanese Patients With Premalignant Lesions After Helicobacter pylori Eradication

Abstract

G A A b st ra ct s culture studies using a transformed (HT29) and non-transformed (YAMC) cell lines to further assess impact of NSAIDs on MUC4. Results: We noted that MUC4 was almost completely lost in human adenocarcinoma as compared to non-neoplastic tissues (99.7% reduction) consistent with our previous immunohistochemical reports. We also noted a dramatic MUC4 loss in the uninvolved tumor field as compared to that of the non-neoplasia tissues (84% reduction). MUC4 was also suppressed in AOM-rat model of colon carcinogenesis,with a 40% loss in uninvolved mucosa. To assess diagnostic potential, we assessed the area under the receiver operator curve (AUROC). The diagnostic capability of MUC4 was good at 0.67 in humans and AUROC=0.83 in AOM-rat. Finally, when we assessed the NSAID celecoxib on HT29 we noted a 318±18% induction of MUC4 (p<0.05) which was comparable to that seen on the non-transformed YAMC (288±13%)with a comparable MUC4 induction (386%±21%)in the sulindac treated AOM rats. Conclusions: We demonstrate, for the first time, that Muc4 is lost in field carcinogenesis. MUC4 loss had an AUROC of 0.67-0.83 making it a promising biomarker for risk-stratification and hence screening. Furthermore, MUC4 was robustly induced by NSAIDS indicating the potential for being an intermediate biomarker for chemoprevention. Further studies are ongoing to assess whether combination with other MUC1 analysis may improve the already very good diagnostic abilities.