Abstract
Abstract
Objective: To investigate Cathepsin B (CTSB) expression in colorectal cancer (CRC) tissues and serum, the association of CTSB expression with tumor stages and metastasis and targeting CTSB by nanoparticles for potential CRC therapeutics.
Methods: CTSB expression was determined in 100 pairs of CRC tumor and adjacent normal tissue using quantitative PCR for mRNA levels. Serum CTSB levels were evaluated in 95 patients and 20 healthy control using enzyme-linked immunosorbant assay (ELISA) technique. Detection of Cathepsin B protein expression in tissues was done using immunohistochemistry and western blotting. Cathepsin B protein expression was inhibited using cobalt oxide nanoparticles in human colorectal cancer cells.
Results: Greater than 90% of tumors had detectable CTSB protein expression with significant increase staining in tumors compared with matched normal colon (p=0.006). The relative levels of CTSB mRNA in tumor samples and adjacent normal colorectal tissue were 0.04 ± 0.06 and 0.01 ± 0.02 respectively. The mRNA expression in early stage CRC compared to late stage CRC was 0.05 ± 0.04 and 0.02 ± 0.01, respectively. Increased mRNA expression was seen in the advanced stages with lymph node metastases compared to control P=0.002. CTSB was significantly higher in sera of patients with lymph node metastasis compared to early and late stage primary tumors. A subset of 40 paired tissue extracts were analyzed by western blotting. This also revealed consistent increase of CTSB protein level in tumor tissue. Treatment of human CRC cell HT-29 with increasing concentrations of cobalt oxide nanoparticles resulted in significant decrease of CTSB expression.
Conclusion: These findings thus indicate that CTSB may be an important prognostic biomarker for early stage CRC and lymph node metastasis in Middle East populations. Monitoring serum CTSB in CRC patient may predict and diagnose lymph node metastasis. Furthermore CTSB may represent a potential target for nanoparticle-based drugs in the treatment of colorectal cancer.
Citation Format: Maha Abdulla. Cathepsin B expression in colorectal cancer in Middle East population: Potential value as a tumor biomarker for late stages. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B06.