2. Academic Validation
  3. Overexpression of SMYD2 contributes to malignant outcome in gastric cancer

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

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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