Analysis of proteasomal subunit expression reveals Rpt4 as a prognostic marker in colorectal cancer

Colorectal cancer is a leading cause of cancer related deaths worldwide. Early diagnosis and treatment is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In this study we examined the protein expression of several key components of the ubiquitin-proteasome system in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 colon cancer patients. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core were predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with better disease free survival (Cox proportional hazard ratio 0.605; p=0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.