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

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Tumor Biology

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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Abbreviations

NNMT:

Nicotinamide N-methyltransferase

NPC:

Nasopharyngeal carcinoma

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Acknowledgments

This work was supported by a grant from Chi Mei Medical Center

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Pathology, Chi-Mei Medical Center, 901 Chunghwa Road, Yung Kang Dist., Tainan County, 710, Taiwan

    Khin Than Win & Chien-Feng Li

  2. Department of Radiation Oncology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan

    Sung-Wei Lee

  3. Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

    Hsuan-Ying Huang

  4. Department of Radiation Oncology, Chi-Mei Medical Center, Tainan, Taiwan

    Li-Ching Lin

  5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan

    Ching-Yih Lin

  6. Department of Leisure, Recreation, and Tourism Management, Tainan, Taiwan

    Ching-Yih Lin

  7. Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan

    Chung-Hsi Hsing

  8. Department of Anesthesiology, College of Medicine, Taipei Medical University, Tainan, Taiwan

    Chung-Hsi Hsing

  9. National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan

    Li-Tzong Chen & Chien-Feng Li

  10. Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

    Li-Tzong Chen

  11. Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Li-Tzong Chen

  12. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chien-Feng Li

  13. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Chien-Feng Li

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  1. Khin Than Win
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Correspondence to Chien-Feng Li.

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Win, K.T., Lee, SW., Huang, HY. et al. Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma. Tumor Biol. 34, 3923–3931 (2013). https://doi.org/10.1007/s13277-013-0980-z

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  • DOI: https://doi.org/10.1007/s13277-013-0980-z

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