Tumor Biology

, Volume 34, Issue 6, pp 3923–3931 | Cite as

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
Research Article


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.


Nasopharyngeal carcinoma NNMT pAkt Prognosis 



Nicotinamide N-methyltransferase


Nasopharyngeal carcinoma



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

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Khin Than Win
    • 1
  • Sung-Wei Lee
    • 2
  • Hsuan-Ying Huang
    • 3
  • Li-Ching Lin
    • 4
  • Ching-Yih Lin
    • 5
    • 6
  • Chung-Hsi Hsing
    • 7
    • 8
  • Li-Tzong Chen
    • 9
    • 10
    • 11
  • Chien-Feng Li
    • 1
    • 9
    • 12
    • 13
  1. 1.Department of PathologyChi-Mei Medical CenterTainan CountyTaiwan
  2. 2.Department of Radiation OncologyChi-Mei Medical CenterTainanTaiwan
  3. 3.Department of Pathology, Kaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
  4. 4.Department of Radiation OncologyChi-Mei Medical CenterTainanTaiwan
  5. 5.Division of Gastroenterology and Hepatology, Department of Internal MedicineChi-Mei Medical CenterTainanTaiwan
  6. 6.Department of Leisure, Recreation, and Tourism ManagementTainanTaiwan
  7. 7.Department of AnesthesiologyChi-Mei Medical CenterTainanTaiwan
  8. 8.Department of AnesthesiologyCollege of Medicine, Taipei Medical UniversityTainanTaiwan
  9. 9.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan
  10. 10.Department of Internal MedicineNational Cheng Kung University HospitalTainanTaiwan
  11. 11.Department of Internal Medicine and Cancer Center, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  12. 12.Institute of Clinical MedicineKaohsiung Medical UniversityKaohsiungTaiwan
  13. 13.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainanTaiwan

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