Overexpression of SETDB1 in relation to poor outcome in gastric carcinoma.

Abstract

71 Background: SETDB1 is a Histone H3 lysine 9-specific Methyl Transferase belonging to the SET domain. In this study, we tested whether SETDB1 acts as a cancer-promoting gene through its overexpression in gastric cancer (GC). Methods: We analyzed5 GC cell lines and 135 primary GC samples curatively resected in our hospital. Results: Overexpression of the SETDB1 protein was detected in all GC cell lines and primary GC samples (115/135 cases, 85%). Knockdown of SETDB1 using specific siRNA inhibited the proliferation, migration and invasion. Overexpression of the SETDB1 was significantly correlated with lymphatic invasion, deeper tumor depth and higher recurrence rate. Patients with SETDB1-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0041, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SETDB1 was independently associated with worse outcome (P = 0.0178, HR 3.1 (1.20-9.83)). Conclusions: These findings suggest that SETDB1 has a crucial role in tumor cell proliferation and highlight its usefulness as a prognostic factor and potential therapeutic target in GC.