Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.
Affiliation
Centre for Systems Medicine and Department of Physiology and Medical Physics,, Royal College of Surgeons in Ireland, Dublin, Ireland; Department of Surgery,, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland.Issue Date
2012-02-01T10:05:01Z
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Int J Cancer. 2011 Sep 29. doi: 10.1002/ijc.26468.Journal
International journal of cancer. Journal international du cancerDOI
10.1002/ijc.26468PubMed ID
21960357Abstract
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.Language
ENGISSN
1097-0215 (Electronic)0020-7136 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1002/ijc.26468
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