1. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan.
2. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
3. Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
4. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
5. Department of Oral and Maxillofacial Surgery, Chi Mei Medical Center, Tainan, Taiwan.
6. Department of Otolaryngology, Chi Mei Medical Center, Yongkang District, Tainan City, Taiwan
7. Department of Optometry, Chung Hwa University of Medical Technology, Tainan, Taiwan
8. Department of Oral & Maxillofacial Surgery, An Nan Hospital, China Medical University, Tainan, Taiwan
Background: Alpha-methylacyl-CoA racemase (AMACR) is a key enzyme responsible for the metabolism of branched-chain fatty acids. It has been found to be an important prognostic factor in numerous types of cancers. This study was aimed to investigate the expression of AMACR and its prognostic significance in patients with oral squamous cell carcinoma (SCC).
Methods: Analysis of publicly available microarray data of oral SCC revealed that AMACR was significantly upregulated in tumor tissue compared with normal mucosa. We further assessed the protein expression of AMACR in 164 patients with oral SCC by immunohistochemistry. The prognostic impact of AMACR expression and its association with various clinicopathological parameters were statistically analyzed.
Results: AMACR overexpression was significantly associated with advanced tumor status (P=0.001), advanced nodal status (P=0.036), increased vascular invasion (P=0.026) and increased perineural invasion (P=0.004). Patients with high expression level of AMACR had significantly worse disease-specific survival (DSS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) (all P<0.0001). In multivariate analysis, AMACR overexpression was also an independent negative prognostic factor for DSS (hazard ratio [HR]: 4.410, 95% confidence interval [CI]: 2.285-8.511, P<0.001), DMFS (HR: 5.157, 95% CI: 2.756-9.651, P<0.001) and LRFS (HR: 4.462, 95% CI: 2.429-8.198, P<0.001).
Conclusions: High expression of AMACR was not only a key adverse prognostic factor but also a potential therapeutic target in oral SCC.
Keywords: AMACR, squamous cell carcinoma, oral, prognosis, transcriptome