Overexpression of Smyd2 Contributes to Tumor Malignant Potential and Poor Outcomes of Adenocarcinoma of the Esophagogastric Junction

Background SET and MYND domain-containing protein 2 (SMYD2) is a lysine methyltransferase for histone H3, inhibits transactivation activities of P53 and RB1. Several studies revealed that SMYD2 acts as a cancer-promoting gene in various cancers. In this study, to detect a novel therapeutic target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether SMYD2 acted as a cancer-promoting gene through its overexpression in AEG. Methods We analyzed cancer cell lines and 103 primary AEG tumor samples which had been curatively resected in our institution between 2000 and 2010. Results Knockdown of SMYD2 using specific small interfering RNA inhibited proliferation, migration and invasion of SMYD2-overexpressing cells in a TP53 mutation-independent manner. Overexpression of SMYD2 was detected in primary tumor samples (14 out of one 103 cases; 13.6%) and was correlated with lymphatic invasion, venous invasion, deeper tumor invasion and higher rates of lymph node metastasis and recurrence. Patients with SMYD2-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.0149, log-rank test). Moreover, multivariate analysis demonstrated that SMYD2 was independently associated with worse outcome (P = 0.0255, hazard ratio 3.78 (1.19–11.0)). Conclusion These findings suggest that SMYD2 has a crucial role by its overexpression and highlight its utility as a prognostic factor and potential therapeutic target in AEG.