Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma

Khin Than Win, Sung Wei Lee, Hsuan Ying Huang, Li Ching Lin, Ching Yih Lin, Chung Hsi Hsing, Li Tzong Chen, Chien Feng Li

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Abstract

Nicotinamide N-methyltransferase (NNMT) is overexpressed in many human cancers and is associated with poor prognosis. Akt (also known as protein kinase B) is an evolutionarily conserved serine/threonine kinase, serving as a downstream effector of the phosphatidylinositol 3-kinase signaling pathway. NNMT was first identified as a differentially upregulated gene in nasopharyngeal cancer tissues through data mining from published transcriptomic databases. Since no prior study has attempted to evaluate the clinical significance of NNMT or phosphorylated Akt (pAkt) expression in nasopharyngeal cancer, this study explores their expression in a large cohort of patients with nasopharyngeal cancer. The study included 124 nasopharyngeal cancer patients who were free of distant metastasis at initial diagnosis. Pathological slides were reviewed and clinical findings collected. We evaluated the expression of NNMT and pAkt immunohistochemically, stratified them into two groups (high and low expression) and examined the correlation with disease-specific survival (DSS), metastasis-free survival (MeFS), local recurrence-free survival (LRFS), and various clinicopathological factors. NNMT expression was significantly positively associated with pAkt expression. The high expression of both markers was significantly associated with an increment of tumor stage (p = 0.006 and p = 0.006, respectively). High expression of NNMT correlated significantly with a more aggressive clinical course and a significantly shorter DSS. Furthermore, NNMT expression and pAkt expression were strongly predictive of MeFS (p = 0.008; p = 0.0063) and LRFS (p = 0.005; p = 0.0125). In multivariate analysis, high expression of NNMT remained as a robust prognosticator for both end points evaluated. It independently portended inferior DSS (p = 0.02, HR = 1.976) and worse MeFS (p = 0.029, HR = 2.022) after tumor stage (p = 0.033, HR = 2.150; p = 0.028, HR = 2.942, for DSS and LRFS, respectively). We found NNMT positively correlated with pAkt expression and was independent adverse prognosticators of patient survival. NNMT therefore has potential utility as an indicator for prognosis, predicting treatment response to chemotherapy or radiation therapy, and even as a therapeutic target in the future.

Original languageEnglish
Pages (from-to)3923-3931
Number of pages9
JournalTumor Biology
Volume34
Issue number6
DOIs
Publication statusPublished - Dec 2013

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Nicotinamide N-Methyltransferase
Phosphorylation
Survival
Nasopharyngeal Neoplasms
Neoplasm Metastasis
Recurrence
Nasopharyngeal carcinoma
Phosphatidylinositol 3-Kinase
Neoplasms
Proto-Oncogene Proteins c-akt
Data Mining
Protein-Serine-Threonine Kinases

Keywords

  • Nasopharyngeal carcinoma
  • NNMT
  • pAkt
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research

Cite this

Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma. / Win, Khin Than; Lee, Sung Wei; Huang, Hsuan Ying; Lin, Li Ching; Lin, Ching Yih; Hsing, Chung Hsi; Chen, Li Tzong; Li, Chien Feng.

In: Tumor Biology, Vol. 34, No. 6, 12.2013, p. 3923-3931.

Research output: Contribution to journalArticle

Win, Khin Than ; Lee, Sung Wei ; Huang, Hsuan Ying ; Lin, Li Ching ; Lin, Ching Yih ; Hsing, Chung Hsi ; Chen, Li Tzong ; Li, Chien Feng. / Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma. In: Tumor Biology. 2013 ; Vol. 34, No. 6. pp. 3923-3931.
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abstract = "Nicotinamide N-methyltransferase (NNMT) is overexpressed in many human cancers and is associated with poor prognosis. Akt (also known as protein kinase B) is an evolutionarily conserved serine/threonine kinase, serving as a downstream effector of the phosphatidylinositol 3-kinase signaling pathway. NNMT was first identified as a differentially upregulated gene in nasopharyngeal cancer tissues through data mining from published transcriptomic databases. Since no prior study has attempted to evaluate the clinical significance of NNMT or phosphorylated Akt (pAkt) expression in nasopharyngeal cancer, this study explores their expression in a large cohort of patients with nasopharyngeal cancer. The study included 124 nasopharyngeal cancer patients who were free of distant metastasis at initial diagnosis. Pathological slides were reviewed and clinical findings collected. We evaluated the expression of NNMT and pAkt immunohistochemically, stratified them into two groups (high and low expression) and examined the correlation with disease-specific survival (DSS), metastasis-free survival (MeFS), local recurrence-free survival (LRFS), and various clinicopathological factors. NNMT expression was significantly positively associated with pAkt expression. The high expression of both markers was significantly associated with an increment of tumor stage (p = 0.006 and p = 0.006, respectively). High expression of NNMT correlated significantly with a more aggressive clinical course and a significantly shorter DSS. Furthermore, NNMT expression and pAkt expression were strongly predictive of MeFS (p = 0.008; p = 0.0063) and LRFS (p = 0.005; p = 0.0125). In multivariate analysis, high expression of NNMT remained as a robust prognosticator for both end points evaluated. It independently portended inferior DSS (p = 0.02, HR = 1.976) and worse MeFS (p = 0.029, HR = 2.022) after tumor stage (p = 0.033, HR = 2.150; p = 0.028, HR = 2.942, for DSS and LRFS, respectively). We found NNMT positively correlated with pAkt expression and was independent adverse prognosticators of patient survival. NNMT therefore has potential utility as an indicator for prognosis, predicting treatment response to chemotherapy or radiation therapy, and even as a therapeutic target in the future.",
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AU - Lin, Ching Yih

AU - Hsing, Chung Hsi

AU - Chen, Li Tzong

AU - Li, Chien Feng

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N2 - Nicotinamide N-methyltransferase (NNMT) is overexpressed in many human cancers and is associated with poor prognosis. Akt (also known as protein kinase B) is an evolutionarily conserved serine/threonine kinase, serving as a downstream effector of the phosphatidylinositol 3-kinase signaling pathway. NNMT was first identified as a differentially upregulated gene in nasopharyngeal cancer tissues through data mining from published transcriptomic databases. Since no prior study has attempted to evaluate the clinical significance of NNMT or phosphorylated Akt (pAkt) expression in nasopharyngeal cancer, this study explores their expression in a large cohort of patients with nasopharyngeal cancer. The study included 124 nasopharyngeal cancer patients who were free of distant metastasis at initial diagnosis. Pathological slides were reviewed and clinical findings collected. We evaluated the expression of NNMT and pAkt immunohistochemically, stratified them into two groups (high and low expression) and examined the correlation with disease-specific survival (DSS), metastasis-free survival (MeFS), local recurrence-free survival (LRFS), and various clinicopathological factors. NNMT expression was significantly positively associated with pAkt expression. The high expression of both markers was significantly associated with an increment of tumor stage (p = 0.006 and p = 0.006, respectively). High expression of NNMT correlated significantly with a more aggressive clinical course and a significantly shorter DSS. Furthermore, NNMT expression and pAkt expression were strongly predictive of MeFS (p = 0.008; p = 0.0063) and LRFS (p = 0.005; p = 0.0125). In multivariate analysis, high expression of NNMT remained as a robust prognosticator for both end points evaluated. It independently portended inferior DSS (p = 0.02, HR = 1.976) and worse MeFS (p = 0.029, HR = 2.022) after tumor stage (p = 0.033, HR = 2.150; p = 0.028, HR = 2.942, for DSS and LRFS, respectively). We found NNMT positively correlated with pAkt expression and was independent adverse prognosticators of patient survival. NNMT therefore has potential utility as an indicator for prognosis, predicting treatment response to chemotherapy or radiation therapy, and even as a therapeutic target in the future.

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