SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas

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• 作者：Rie Ohtomo-Oda ; MD^a ; ^b ; ^c ; Shuhei Komatsu ; MD ; PhD^d ; Taisuke Mori ; DDS ; PhD^e ; Shigeki Sekine ; MD ; PhD^e ; Shoji Hirajima ; MD^d ; Seiichi Yoshimoto ; MD ; PhD^f ; Yae Kanai ; MD ; PhD^e ; Eigo Otsuji ; MD ; PhD^d ; Eiji Ikeda ; MD ; PhD^b ; Hitoshi Tsuda ; MD ; PhD^a ; ^g ; ^{htsuda@ndmc.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Head and neck squamous cell carcinoma ; HPV unrelated ; SMYD2 ; p53 ; Multiple cancer ; Second primary cancer
• 刊名：Human Pathology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：49
• 期：Complete
• 页码：145-155
• 全文大小：1140 K

文摘

Human papillomavirus (HPV)–unrelated head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease, and there are no suitable prognostic or predictive markers. The SET and MYND domain-containing protein 2 (SMYD2), a lysine methyltransferase for histone H3K36 and p53K370, that regulates transcription was previously found to be a cancer-promoting gene in esophageal squamous cell carcinoma. In this study, we investigated whether SMYD2 is a possible oncogene and a prognostic indicator in HPV-unrelated, multiple and nonmultiple HNSCC. Among 197 HPV-unrelated HNSCC cases, overexpression of SMYD2 protein was detected in 75 (60%) of 126 nonmultiple cases and 51 (70%) of 71 multiple cases. In nonmultiple cases, patients with SMYD2-overexpressing tumors had a worse overall survival rate than did those with nonexpressing tumors (P = .017, log-rank test), and SMYD2 positivity was independently associated with overall survival in the multivariate analysis (P = .003). In both nonmultiple and multiple groups, the combination of SMYD2 and p53 immunopositivity was a significant prognostic indicator (P = .027 and .015). In 5 HNSCC cell lines, overexpression of SMYD2 messenger RNA and protein was observed, but there was no notable amplification at 1q32-41.1. The proliferation of UM-SCC-17B HPV-unrelated HNSCC cell line was inhibited by knockdown of SMYD2 gene expression. These findings suggest that SMYD2 plays a role in tumor progression and might be a useful prognosticator in HPV-unrelated, nonmultiple HNSCC.