Endoplasmic reticulum aminopeptidase 2 involvement in metastasis of oral cavity squamous cell carcinoma discovered by proteome profiling of primary cancer cells

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 OSCCassociated protein. Compared with the adjacent normal tissues, ERAP2 levels were determined to be significantly elevated in OSCC tissues using quantitative realtime 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.