BUBR1 as a Prognostic Biomarker in Canine Oral Squamous Cell Carcinoma

SIMPLE SUMMARY: Spindle assembly checkpoint (SAC) includes several proteins that can be dysregulated contributing to oral carcinogenesis. We have investigated the role of some SAC components (BUBR1, BUB3 and SPINDLY proteins) in canine oral squamous cell carcinoma (OSCC) by immunohistochemical analysis of 60 canine OSCCs. We observed that all proteins were detected in almost all cases and with a high expression rate in some cases. Furthermore, we found an independent prognostic value for BUBR1, where high BUBR1 expression was associated with a lower survival rate of these canine patients. These results suggest a potential role of BUBR1 as a prognostic biomarker in canine OSCC and should motivate further studies aimed at the role of these SAC proteins not only as biomarkers but also as pharmacological targets in canine OSCC. ABSTRACT: Chromosomal instability (CIN) plays a key role in the carcinogenesis of several human cancers and can be related to the deregulation of core components of the spindle assembly checkpoint (SAC) including BUBR1 protein kinase. These proteins have been related to tumor development and poor survival rates in human patients with oral squamous cell carcinoma (OSCC). To investigate the expression of the SAC proteins BUBR1, BUB3 and SPINDLY and also Ki-67 in canine OSCC, we performed an immunohistochemical evaluation in 60 canine OSCCs and compared them with clinical and pathological variables. BUBR1, Ki-67, BUB3 and SPINDLY protein expressions were detected in all cases and classified as with a high-expression extent score in 31 (51.7%) cases for BUBR1, 33 (58.9%) cases for BUB3 and 28 (50.9%) cases for SPINDLY. Ki-67 high expression was observed in 14 (25%) cases. An independent prognostic value for BUBR1 was found, where high BUBR1 expression was associated with lower survival (p = 0.012). These results indicate that BUBR1 expression is an independent prognostic factor in these tumors, suggesting the potential use for clinical applications as a prognostic biomarker and also as a pharmacological target in canine OSCC.