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Tumor Biology

, Volume 34, Issue 2, pp 759–768 | Cite as

Fatty acid synthase overexpression confers an independent prognosticator and associates with radiation resistance in nasopharyngeal carcinoma

  • Yu-Chien Kao
  • Sung-Wei Lee
  • Li-Ching Lin
  • Li-Tzong Chen
  • Chung-Hsi Hsing
  • Han-Ping Hsu
  • Hsuan-Ying Huang
  • Yow-Ling Shiue
  • Tzu-Ju Chen
  • Chien-Feng Li
Research Article

Abstract

Fatty acid synthase (FASN) is overexpressed in many human cancers and associated with poor prognosis. However, the role of FASN in nasopharyngeal carcinoma (NPC) has not been studied. We evaluated the expression of FASN immunohistochemically in 124 NPC specimens, stratified them into two groups (FASN-high and FASN-low), and examined the correlation with various clinicopathological parameters. In two NPC cell lines, HONE1 and TW01, we targeted the FASN transcript by shRNAi and evaluated the effect on cell proliferation by WST-1 assay and radiation-induced apoptosis by measuring caspase-3 and caspase-7 activation. NPC with high FASN immunoexpression was correlated with advanced pT disease status and worse prognosis in terms of disease-specific survival, metastasis-free survival and local recurrence-free survival, compared to FASN-low group in both univariate and multivariate analyses. In the two NPC cell lines, endogenous FASN expression was significantly higher than the non-tumor keratinocyte, DOK. When the expression of FASN was suppressed by shRNAi, the tumor cells showed decreased cell proliferation and increased apoptosis after radiation. Our results supported FASN as an adverse prognostic marker in NPC, possibly by conferring cell growth advantage and resistance to radiation-induced apoptosis on tumor cells. The inhibition of FASN expression might be investigated as an adjunct in treatment, especially in radiation resistant NPC.

Keywords

Fatty acid synthase Nasopharyngeal carcinoma Radiation resistance 

Abbreviations

FASN

Fatty acid synthase

NPC

Nasopharyngeal carcinoma

Notes

Acknowledgements

This work was supported by a grant from Taipei Medical University (101swf04 to Y.C. Kao and C.F. Li).

Conflicts of interest

None

Authors' contributions

YC Kao and TJ Chen carried out the molecular genetic studies. SW Lee, HP Hsu and CH Hsing carried out the immunostaining and slide reading. LC Lin, HY Huang, YL Shiue, and LT Chen participated in the design of the study and performed the statistical analysis. CF Li conceived of the study, and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Yu-Chien Kao
    • 1
    • 2
  • Sung-Wei Lee
    • 3
  • Li-Ching Lin
    • 4
  • Li-Tzong Chen
    • 5
    • 6
    • 7
    • 8
  • Chung-Hsi Hsing
    • 9
    • 10
  • Han-Ping Hsu
    • 11
  • Hsuan-Ying Huang
    • 12
  • Yow-Ling Shiue
    • 13
  • Tzu-Ju Chen
    • 14
  • Chien-Feng Li
    • 5
    • 14
    • 15
    • 16
  1. 1.Department of Pathology, Wan Fang HospitalTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Pathology, Shuang Ho HospitalTaipei Medical UniversityTaipeiTaiwan
  3. 3.Department of Radiation OncologyChi-Mei Medical Center, LiouyingTainanTaiwan
  4. 4.Department of Radiation OncologyChi Mei Medical CenterTainanTaiwan
  5. 5.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan
  6. 6.Department of Internal MedicineNational Cheng Kung University HospitalTainanTaiwan
  7. 7.Institute of Molecular MedicineNational Cheng Kung UniversityTainanTaiwan
  8. 8.Department of Internal MedicineKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
  9. 9.Department of AnesthesiologyChi Mei Medical CenterTainanTaiwan
  10. 10.Department of AnesthesiologyCollege of Medicine, Taipei Medical UniversityTaipeiTaiwan
  11. 11.College of MedicineChina Medical UniversityTaichungTaiwan
  12. 12.Departments of PathologyKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiungTaiwan
  13. 13.Institute of Biomedical ScienceNational Sun Yat-Sen UniversityKaohsiungTaiwan
  14. 14.Department of PathologyChi Mei Medical CenterTainanTaiwan
  15. 15.Department of Medical TechnologyChung Hwa University of Medical TechnologyTainanTaiwan
  16. 16.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainanTaiwan

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