Overexpression of SMYD2 in gastric cancer
Komatsu, S Kyoto Prefectural University of Medicine
Ichikawa, D Kyoto Prefectural University of Medicine
Hirajima, S Kyoto Prefectural University of Medicine
Nagata, H Kyoto Prefectural University of Medicine
Nishimura, Y Kyoto Prefectural University of Medicine
Kawaguchi, T Kyoto Prefectural University of Medicine
Miyamae, M Kyoto Prefectural University of Medicine
Okajima, W Kyoto Prefectural University of Medicine
Ohashi, T Kyoto Prefectural University of Medicine
Konishi, H Kyoto Prefectural University of Medicine
Shiozaki, A Kyoto Prefectural University of Medicine
Fujiwara, H Kyoto Prefectural University of Medicine
Okamoto, K Kyoto Prefectural University of Medicine
Tsuda, H National Cancer Center Hospital
Inazawa, J Tokyo Medical and Dental University
Otsuji, E Kyoto Prefectural University of Medicine
Background: SET and MYND domain-containing protein 2 (SMYD2) is a lysine methyltransferase for histone H3, p53 and Rb and inhibits their transactivation activities. In this study, we tested whether SMYD2 (1q42) acts as a cancer-promoting factor by being overexpressed in gastric cancer.
Methods: We analysed 7 gastric cancer cell lines and 147 primary tumor samples of gastric cancer, which were curatively resected in our hospital.
Results: SET and MYND domain-containing protein 2 was detected in these cell lines (five out of seven cell lines; 71.4%) and primary tumor samples (fifty-six out of one hundred and forty-seven cases; 38.1%). 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 protein correlated with larger tumor size, more aggressive lymphatic invasion, deeper tumor invasion and higher rates of lymph node metastasis and recurrence. Patients with SMYD2-overexpressing tumours had a worse overall rate of survival than those with non-expressing tumours (P=0.0073, log-rank test) in an intensity and proportion score-dependent manner. Moreover, multivariate analysis demonstrated that SMYD2 was independently associated with worse outcome (P=0.0021, hazard ratio 4.25 (1.69–10.7)).
Conclusions: These findings suggest that SMYD2 has a crucial role in tumor cell proliferation by its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer.
British Journal of Cancer
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