title: Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.
abstract: Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer 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 our study, we examined the protein expression of several key components of the UPS 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 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was 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 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.
authors.affiliation: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: McCawley
authors.forename: Susan
authors.initials: S
authors.lastname: Conlon
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hector
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cummins
authors.forename: Patrick
authors.initials: P
authors.lastname: Dicker
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Johnston
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.forename: Deborah A
authors.initials: DA
authors.lastname: McNamara
authors.forename: Jochen H M
authors.initials: JH
authors.lastname: Prehn
authors.forename: Caoimhín G
authors.initials: CG
authors.lastname: Concannon
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D046988:Proteasome Endopeptidase Complex