Abstract
Abstract Background: Ceramide synthase 5 (CerS5) is multi-pass transmembrane protein of the endoplasmic reticulum. Functioning as a bona fide (dihydro)ceramide synthase, CerS5 regulates the levels of short ceramide species. Ceramides are bioactive lipids implicated in proliferation, senescence, angiogenesis and death of normal and cancerous cells. We aimed to investigate CerS5 expression in colorectal cancer tissue and to evaluate the prognostic significance of CerS5 in colorectal cancer patients. Methods: CerS5 expression was analyzed by immunohistochemistry on tissue microarrays constructed from 125 colorectal cancer patients. The associations between CerS5 staining and the clinicopathological factors were examined using the Spearman rank correlation test. Patient survival was examined using the Kaplan-Meier survival analysis and Cox proportional hazard modeling, categorized according to high or low CerS5 staining intensity. Results: Immunohistological staining revealed an overexpression of membranous CerS5 in 63 out of 125 (50.4%) colorectal carcinomas. CerS5 overexpression significantly correlated with lymphovascular invasion and metastatic disease in matched tumor cases (P = 0.036 & P = 0.037, respectively). Patients with CerS5 overexpressing tumors had a significantly lower overall 5-year survival (OS, P = 0.029) and 5-year recurrence-free survival (RFS, P = 0.047). Cox multivariate analysis showed that the increased CerS5 expression was an independent predictor of OS (hazard ratio (HR) = 1.604; 95% confidence interval (CI) 1.010-2.548, P = 0.045) and RFS (HR = 1.592; CI 1.036-2.447, P = 0.034). Conclusions: We found an increased expression of ceramide synthase 5 (CerS5) in 50% of investigated colorectal carcinomas, which was associated with lymphovascular invasion, metastasis and poor survival in colorectal cancer patients. Our study identifies CerS5 as a novel independent prognostic biomarker for patients with colorectal cancer. Citation Format: Seán Fitzgerald, Katherine M. Sheehan, Anthony O'Grady, Dermot Kenny, Richard O'Kennedy, Elaine W. Kay, Gregor Kijanka. Increased ceramide synthase 5 expression is associated with lymphovascular invasion, metastasis and poor survival in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1159. doi:10.1158/1538-7445.AM2013-1159
Published Version
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