SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas
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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DOI：
10.1016/j.humpath.2015.08.025
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发表时间：
2016-03-01
期刊：
影响因子：
3.3
通讯作者：
Tsuda, Hitoshi
中科院分区：
文献类型：
--
作者：
Ohtomo-Oda, Rie;Komatsu, Shuhei;Tsuda, Hitoshi
人乳头瘤病毒（HPV）无关的头颈部鳞状细胞癌（HNSCC）是一种异质性疾病，没有合适的预后或预测标志物。SET和MYND结构域蛋白2（SMYD 2）是一种调节组蛋白H31 β 6和p53 K370转录的赖氨酸甲基转移酶，以前被发现是食管鳞状细胞癌中的促癌基因。在这项研究中，我们调查了SMYD 2是否是一个可能的癌基因，并在HPV无关，多发性和非多发性HNSCC的预后指标。在197例与HPV无关的HNSCC中，SMYD 2蛋白在126例非多发性HNSCC中的75例（60%）和71例多发性HNSCC中的51例（70%）中过度表达。在非多发性病例中，SMYD 2过表达肿瘤患者的总生存率低于非表达肿瘤患者（P = 0.017，对数秩检验），多变量分析中SMYD 2阳性与总生存率独立相关（P = 0.003）。在非多组和多组中，SMYD 2和p53免疫阳性的组合是一个重要的预后指标（P = 0.027和0.015）。在5个HNSCC细胞系中，观察到SMYD 2信使RNA和蛋白的过表达，但在1 q32 -41.1没有明显扩增。SMYD 2基因表达下调可抑制UM-SCC-17 B HPV非相关性HNSCC细胞系的增殖。这些发现表明SMYD 2在肿瘤进展中起作用，并且可能是HPV无关的非多发性HNSCC中有用的预测因子。(C)2015 Elsevier Inc. All rights reserved.
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 H31(36 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, over expression 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. (C) 2015 Elsevier Inc. All rights reserved.