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 output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7983-7991
Number of pages9
JournalTumor Biology
Volume35
Issue number8
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Survival
Neoplasm Metastasis
Recurrence
alpha-methylacyl-CoA racemase
Nasopharyngeal carcinoma
Data Mining
Reverse Transcription
Neoplasms
Prostatic Neoplasms
Fatty Acids
Therapeutics
Joints
Western Blotting
Immunohistochemistry
Databases
Carcinoma
Biopsy
Polymerase Chain Reaction
Enzymes
Genes

Keywords

  • AMACR
  • Nasopharyngeal carcinoma
  • Prognosis
  • Transcriptome

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)

Cite this

Lee, Y. E., He, H. L., Lee, S. W., Chen, T. J., Chang, K. Y., Hsing, C. H., & Li, C. F. (2014). AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. Tumor Biology, 35(8), 7983-7991. https://doi.org/10.1007/s13277-014-2065-z

AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. / Lee, Ying En; He, Hong Lin; Lee, Sung Wei; Chen, Tzu Ju; Chang, Kwang Yu; Hsing, Chung Hsi; Li, Chien Feng.

In: Tumor Biology, Vol. 35, No. 8, 2014, p. 7983-7991.

Research output: Contribution to journalArticle

Lee, YE, He, HL, Lee, SW, Chen, TJ, Chang, KY, Hsing, CH & Li, CF 2014, 'AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma', Tumor Biology, vol. 35, no. 8, pp. 7983-7991. https://doi.org/10.1007/s13277-014-2065-z
Lee, Ying En ; He, Hong Lin ; Lee, Sung Wei ; Chen, Tzu Ju ; Chang, Kwang Yu ; Hsing, Chung Hsi ; Li, Chien Feng. / AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma. In: Tumor Biology. 2014 ; Vol. 35, No. 8. pp. 7983-7991.
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