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Tumor Biology

, Volume 35, Issue 8, pp 7983–7991 | Cite as

AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma

  • Ying-En Lee
  • Hong-Lin He
  • Sung-Wei Lee
  • Tzu-Ju Chen
  • Kwang-Yu Chang
  • Chung-Hsi Hsing
  • Chien-Feng Li
Research Article

Abstract

The molecular prognostic adjunct in patients with nasopharyngeal carcinomas (NPCs) still remains obscured. Through data mining from published transcriptomic database, alpha-methylacyl-CoA racemase (AMACR) was first identified as a differentially upregulated gene in NPC tissues, which is a key enzyme for isometric conversion of fatty acids entering the β-oxidation. Given the roles of AMACR in prognostication and frontline therapeutic regimen of common carcinomas, such as prostate cancer, we explored AMACR immunoexpression status and its clinical significance in NPC patients. AMACR immunohistochemistry was retrospectively performed and analyzed using H-score for biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as featuring AMACR overexpression. The findings were correlated with the clinicopathological variables, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Endogenous AMACR protein expressions were assessed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting in NPC cells and non-neoplastic mucosal cells. AMACR overexpression was significantly associated with increment of primary tumor status (P = 0.009) and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS. In the multivariate comparison, AMACR overexpression still remained prognostically independent to portend worse DSS (P = 0.006, hazard ratio = 2.129), DMFS (P = 0.001, hazard ratio = 2.795), and LRFS (P = 0.041, hazard ratio = 2.009), together with advanced American Joint of Cancer Committee (AJCC) stages III–IV. Compared with non-neoplastic cells, both HONE1 and TW01 NPC cells demonstrated markedly increased AMACR expression. AMACR overexpression was identified as an important prognosticator and a potential therapeutic target in the future.

Keywords

Nasopharyngeal carcinoma Transcriptome AMACR Prognosis 

Notes

Acknowledgments

This study was supported by a grant from the Ministry of Health and Welfare (MOHW103-TD-B-111-05) to C-F. Li. The authors also thank Biobank at Chi-Mei Medical Center for providing the tumor samples.

Conflicts of interest

None

Authors’ contributions

Conception and design: C-F. Li, Y-E. Lee, H-L. He

Development of methodology: C-F. Li, K-Y. Chang, S-W. Lee

Acquisition of data: S-W Lee, T-J Chen, H-L. He

Analysis and interpretation of data: C-F. Li, S-W. Lee

Writing and/or revision of the manuscript: C-F. Li, Y-E. Lee

Study supervision: C-F. Li, C-H. Hsing

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ying-En Lee
    • 1
  • Hong-Lin He
    • 2
  • Sung-Wei Lee
    • 3
  • Tzu-Ju Chen
    • 4
  • Kwang-Yu Chang
    • 5
  • Chung-Hsi Hsing
    • 6
  • Chien-Feng Li
    • 4
    • 5
    • 7
    • 8
  1. 1.Department of AnesthesiologyKaohsiung Chang Gung Memorial Hospital and Chang Gung University College of MedicineKaohsiungTaiwan
  2. 2.Department of PathologyE-DA Hospital, I-Shou UniversityKaohsiungTaiwan
  3. 3.Department of Radiation OncologyChi-Mei Medical CenterTainanTaiwan
  4. 4.Department of PathologyChi-Mei Medical CenterTainanTaiwan
  5. 5.National Institute of Cancer ResearchNational Health Research InstitutesTainanTaiwan
  6. 6.Department of AnesthesiologyChi-Mei Medical CenterTainanTaiwan
  7. 7.Department of BiotechnologySouthern Taiwan University of Science and TechnologyTainanTaiwan
  8. 8.Institute of Clinical MedicineKaohsiung Medical UniversityKaohsiungTaiwan

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