Abstract 3986: Diagnostic significance of cathepsin L and cathepsin B expression in human gallbladder cancer - A pilot study

Abstract

Abstract Background: Gallbladder cancer (GBC) is the most common biliary tract malignancy worldwide. Cancer of gallbladder usually refers to as an Indian disease as it is more common in Indian subcontinent especially in north and central India. Incidence rate of GBC in women in Delhi is as high as 21.5 per 100,000 population. It is an aggressive malignancy, which spreads locally to liver, adjacent organs and lymph nodes as well as to distant organs. Cathepsin L (CTSL) and B (CTSB) are lysosomal cysteine proteases implicated in protein turnover and tissue remodeling. Deregulated expression of these proteases has been associated with invasion and metastasis in several solid tumors. Objective: To assess the expression and clinical significance of CTSL and CTSB in human gallbladder cancer. Methods: We assayed the activities of CTSL and CTSB via spectroflurometrically in whole tissue lysates of gallbladder cancer patients (N = 23) and normal gall bladder tissue samples with gallstones (N = 31) / without gallstones (N = 34), which served as controls. Activities of these proteases were correlated with several clinic pathological parameters in GBC patients. CTSL and CTSB mRNA levels were determined in tissues samples by Real time PCR. Furthermore serum levels of these proteases were also assayed using sandwich based ELISA in GBC patients and controls. Results: Significant increase in the enzymatic activities of CTSL+B, CTSL and CTSB was observed in gallbladder cancer tissue samples in comparison to normal gall bladder both with and without gallstones (p < 0.001). ROC analysis confirmed the diagnostic relevance of CTSL and CTSB analysis with area under the curve 0.791 and 0.840 respectively for gallbladder cancer patients with respect to controls. Over expression of CTSB was also significantly associated with involvement of lymph node (p = 0.05) in gall bladder carcinoma. Secretory levels of CTSL and CTSB in serum were significantly elevated in GBC patients (p <0.01). Increased expression of these cysteine proteases were also confirmed at the mRNA level by Real time PCR. Conclusion: Our study for the first time demonstrated a significant increase in the levels of cathepsin L and B in GBC patients as compared to controls. Elevated levels of these proteases may serve as potential biomarkers for human gall bladder cancer. Citation Format: SIDDHARTH MEHRA, MANISH KUMAR, RAJESH PANWAR, NIHAR RANJAN DASH, RATNAKAR SINGH, RAJNI YADAV, SIDDHARTHA DATTA GUPTA, PEUSH SAHNI, SHYAM S. CHAUHAN. Diagnostic significance of cathepsin L and cathepsin B expression in human gallbladder cancer - A pilot study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3986.