Overexpression of SMYD2 contributes to malignant outcome in gastric cancer.
Overexpression of SMYD2 contributes to malignant outcome in gastric cancer.
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DOI：
10.1038/bjc.2014.543
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发表时间：
2015-01-20
影响因子：
8.8
通讯作者：
Otsuji E
中科院分区：
文献类型：
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作者：
Komatsu S;Ichikawa D;Hirajima S;Nagata H;Nishimura Y;Kawaguchi T;Miyamae M;Okajima W;Ohashi T;Konishi H;Shiozaki A;Fujiwara H;Okamoto K;Tsuda H;Imoto I;Inazawa J;Otsuji E
SET和MYND结构域蛋白2（SMYD 2）是一种组蛋白H3、p53和Rb的赖氨酸甲基转移酶，并抑制它们的反式激活活性。在这项研究中，我们测试了SMYD 2（1 q42）是否通过在胃癌中过表达而作为促癌因子。本文分析了7株胃癌细胞系和147例胃癌原发灶标本。在这些细胞系（7个细胞系中的5个; 71.4%）和原发性肿瘤样品（147个病例中的五十六个; 38.1%）中检测到含SET和MYND结构域的蛋白2。使用特异性小干扰RNA敲低SMYD 2以TP 53突变非依赖性方式抑制SMYD 2过表达细胞的增殖、迁移和侵袭。SMYD 2蛋白的过表达与肿瘤体积增大、淋巴结浸润性增强、肿瘤浸润深度增加、淋巴结转移和复发率增高有关。SMYD 2过表达肿瘤患者的总体生存率比非表达肿瘤患者差（P=0.0073，对数秩检验），且具有强度和比例评分依赖性。此外，多变量分析表明SMYD 2与不良结局独立相关（P=0.0021，风险比4.25（1.69-10.7））。这些发现表明SMYD 2通过其过表达在肿瘤细胞增殖中具有关键作用，并突出了其作为胃癌预后因子和潜在治疗靶点的有用性。
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. We analysed 7 gastric cancer cell lines and 147 primary tumor samples of gastric cancer, which were curatively resected in our hospital. 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)). 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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