Sa1693 Cathepsin-B in Colon Cancer: Gene Expression and Clinical Evaluation

Abstract

INTRODUCTION. Colon cancer (CC) remains the third leading cause of worldwide cancerrelated death in men and women. Currently, available prognostic and/or predictive markers for colon cancer lack specificity and sensitivity. Developing new biomarker for early detection, accurate diagnosis and therapeutic treatment for CC is of great importance in improving the clinical outcome of the disease. Cathepsin B (CB), a lysosomal cysteine protease, is expressed constitutively in lysosomes, however its expression and localization change in cancer. High levels of expression of CB at both gene and protein levels have been observed in different types of cancer. AIM. The aim of this study was to analyze the CB expression in different stages of CC progression and to evaluate its clinical relevance. MATERIALS & METHODS. We examined for first time, using quantitative real time PCR, the expression of CB in 185 colonic tissue specimens from 130 patients; 50 were pairs of cancerous-normal tissues, 17 were cancerous tissues and 63 were adenomas for 5 of which normal paired mucosa were also available. RESULTS. We proved that CB was up regulated in the cancer specimens in comparison to their normal pairedmucosa (p<0.001), as well as in the adenomas in comparison to normal tissue (p<0.001). CB expression was found to be associated with histological grade (p=0.037). Cox proportional hazard regression model using univariate and multivariate analysis revealed that high status CB expression is a significant factor for disease-free survival(DFS) (p=0.037 and 0.0038, respectively) and overall survival (OS)(p= 0.003 and p=0.0037, respectively) of patients. Receiver-operating characteristic (ROC) analysis of our results showed that CB has discriminatory value between CC and adenomas tissues (area under the curve [AUC]=0.711). Kaplan-Meier survival curves demonstrated that CB expression of low status is significantly associated with longer DFS (p=0.023) as well as OS (p=0.002). CONCLUSION. Present results suggest that CB gene expression may represent a useful marker of unfavorable prognosis for CC patients with discriminatory power between CC and adenoma patients.