Endoplasmic reticulum aminopeptidase 2 involvement in metastasis of oral cavity squamous cell carcinoma discovered by proteome profiling of primary cancer cells
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I-Chun Kuo1,*, Huang-Kai Kao2,3,*, Yenlin Huang4, Chun-I Wang1, Jui-Shan Yi1,5, Ying Liang5, Chun-Ta Liao1,3, Tzu-Chen Yen3,6, Chih-Ching Wu1,5,7 and Kai-Ping Chang1,3,5
1Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan
2Department of Plastic & Reconstructive Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan
3College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan
4Departments of Pathology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan
5Molecular Medicine Research Center, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan
6Departments of Nuclear Medicine, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan
7Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan
*These authors have contributed equally to this work
Kai-Ping Chang, email: [email protected]
Chih-Ching Wu, email: [email protected]
Keywords: OSCC, proteome, metastasis, prognosis, ERAP2
Received: September 30, 2016 Accepted: May 23, 2017 Published: June 27, 2017
Oral cavity squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide and associated with poor prognosis and mortality. Discovery of proteins that can improve OSCC treatment is needed. Using comparative proteome profiling of primary cells derived from OSCC and adjacent noncancerous epithelium, endoplasmic reticulum aminopeptidases 2 (ERAP2) has been identified as an OSCC-associated protein. Compared with the adjacent normal tissues, ERAP2 levels were determined to be significantly elevated in OSCC tissues using quantitative real-time PCR and immunohistochemistry. Importantly, overexpression of ERAP2 was associated with positive N stage, advanced overall stage, positive perineural invasion, and tumor depth (P = 0.041, 0.015, 0.010, and 0.032, respectively). The overall survival rates of patients without and with the ERAP2 overexpression were 71.9% and 56.0%, respectively (P = 0.029). Furthermore, knockdown of ERAP2 inhibited the migration and invasion abilities of OSCC cells. Our results collectively show that ERAP2 overexpression is associated with the cervical metastasis and poorer prognosis of OSCC.
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