Ubiquitin-Specific Peptidase 22, a Histone Deubiquitinating Enzyme,Is a Novel Poor Prognostic Factor for Salivary Adenoid Cystic Carcinoma

Salivary Adenoid Cystic Carcinoma (SACC) is characterized by a high rate of local recurrence and infiltration, strong invasion to peripheral nerves or late distant metastasis. Our aim was to investigate the expression of Ubiquitin-specific protease 22 (USP22) in SACC patients and its possible relationship to the outcome of the disease. A total of 135 SACC tissues and adjacent non-cancerous tissues which were diagnosed between 2002 and 2007 were enrolled in this study. Immunohistochemistry was used to compare the expression pattern of USP22 in SACC and adjacent non-cancerous groups, and the prognostic significance was assessed by Kaplan-Meier analysis and Cox proportional hazards regression in SACC patients. The rate of high expression of USP22 was significantly higher in SACC group than that in adjacent non-cancerous group. High expression of USP22 was significantly correlated with histological subtype, lymph node metastasis, grade, Ki-67 and SOX2 expression. Furthermore, USP22 acts as an oncogene by regulation the BMI-1 pathway and c-Myc pathway. SACC patients with high USP22 expression showed the poorer overall survival (OS) and disease-free survival (DFS) than those patients with low USP22 expression. In multivariate analysis, only lymph node metastasis and USP22 expression were the independent prognostic factors for OS and DFS in SACC. Our study provides evidence that USP22 expression is an independent prognostic factor for SACC patients.