Overexpression of SMYD2 contributes to malignant outcome in gastric cancer

  • Br J Cancer. 2015 Jan 20;112(2):357-64. doi: 10.1038/bjc.2014.543.
S Komatsu  1 ,  D Ichikawa  1 ,  S Hirajima  1 ,  H Nagata  1 ,  Y Nishimura  1 ,  T Kawaguchi  1 ,  M Miyamae  1 ,  W Okajima  1 ,  T Ohashi  1 ,  H Konishi  1 ,  A Shiozaki  1 ,  H Fujiwara  1 ,  K Okamoto  1 ,  H Tsuda  2 ,  I Imoto  3 ,  J Inazawa  4 ,  E Otsuji  1
Affiliations
  • 1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachihirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
  • 2. Department of Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan.
  • 3. Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8505, Japan.
  • 4. Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo 113-5810, Japan.
PMID: 25321194 DOI: 10.1038/bjc.2014.543
Abstract

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.

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