AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma.
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.
Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Ying-En
YE
Lee
Hong-Lin
HL
He
Sung-Wei
SW
Lee
Tzu-Ju
TJ
Chen
Kwang-Yu
KY
Chang
Chung-Hsi
CH
Hsing
Chien-Feng
CF
Li
D000328:Adult; D000368:Aged; D002277:Carcinoma; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D019998:Racemases and Epimerases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012189:Retrospective Studies
D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase