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

Rie Ohtomo-Oda, Shuhei Komatsu, Taisuke Mori, Shigeki Sekine, Shoji Hirajima, Seiichi Yoshimoto, Yae Kanai, Eigo Otsuji, Eiji Ikeda, Hitoshi Tsuda

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)145-155
Number of pages11
JournalHuman Pathology
Volume49
DOIs
Publication statusPublished - 2016 Mar 1
Externally publishedYes

Fingerprint

Neck
Head
Cell Proliferation
Carcinoma
Neoplasms
Histone-Lysine N-Methyltransferase
Protein Domains
Cell Line
Neoplasm Genes
Oncogenes
Carcinoma, squamous cell of head and neck
Proteins
Multivariate Analysis
Survival Rate
Gene Expression
Messenger RNA
Survival

Keywords

  • Head and neck squamous cell carcinoma
  • HPV unrelated
  • Multiple cancer
  • p53
  • Second primary cancer
  • SMYD2

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas. / Ohtomo-Oda, Rie; Komatsu, Shuhei; Mori, Taisuke; Sekine, Shigeki; Hirajima, Shoji; Yoshimoto, Seiichi; Kanai, Yae; Otsuji, Eigo; Ikeda, Eiji; Tsuda, Hitoshi.

In: Human Pathology, Vol. 49, 01.03.2016, p. 145-155.

Research output: Contribution to journalArticle

Ohtomo-Oda, Rie ; Komatsu, Shuhei ; Mori, Taisuke ; Sekine, Shigeki ; Hirajima, Shoji ; Yoshimoto, Seiichi ; Kanai, Yae ; Otsuji, Eigo ; Ikeda, Eiji ; Tsuda, Hitoshi. / SMYD2 overexpression is associated with tumor cell proliferation and a worse outcome in human papillomavirus-unrelated nonmultiple head and neck carcinomas. In: Human Pathology. 2016 ; Vol. 49. pp. 145-155.
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AU - Komatsu, Shuhei

AU - Mori, Taisuke

AU - Sekine, Shigeki

AU - Hirajima, Shoji

AU - Yoshimoto, Seiichi

AU - Kanai, Yae

AU - Otsuji, Eigo

AU - Ikeda, Eiji

AU - Tsuda, Hitoshi

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N2 - 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.

AB - 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.

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