Cathepsin B expression in colorectal cancer in a Middle East population: Potential value as a tumor biomarker for late disease stages

Abdulla,Maha-Hamadien; Valli-Mohammed,Mansoor-Ali; Al-Khayal,Khayal; Al Shkieh,Abdulmalik; Zubaidi,Ahmad; Ahmad,Rehan; Al-Saleh,Khalid; Al-Obeed,Omar; McKerrow,James

doi:10.3892/or.2017.5576

Cathepsin B expression in colorectal cancer in a Middle East population: Potential value as a tumor biomarker for late disease stages

Authors:
- Maha-Hamadien Abdulla
- Mansoor-Ali Valli-Mohammed
- Khayal Al-Khayal
- Abdulmalik Al Shkieh
- Ahmad Zubaidi
- Rehan Ahmad
- Khalid Al-Saleh
- Omar Al-Obeed
- James McKerrow
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Affiliations: Colorectal Research Chair, Department of Surgery, King Khalid University Hospital, King Saud University, College of Medicine, Riyadh 11472, Kingdom of Saudi Arabia, Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh 11472, Kingdom of Saudi Arabia, Medical Oncology Unit, Department of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093, USA
Published online on: April 18, 2017 https://doi.org/10.3892/or.2017.5576
Pages: 3175-3180
Copyright: © Abdulla et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cathepsin B (CTSB), is a cysteine protease belonging to the cathepsin (Clan CA) family. The diagnostic and prognostic significance of increased CTSB in the serum of cancer patients have been evaluated for some tumor types. CTSB serum and protein levels have also been reported previously in colorectal cancer (CRC) with contradictory results. The aim of the present study was to investigate CTSB expression in CRC patients and the association of CTSB expression with various tumor stages in a Middle East population. Serum CTSB levels were evaluated in 70 patients and 20 healthy control subjects using enzyme-linked immunosorbant assay (ELISA) technique. CTSB expression was determined in 100 pairs of CRC tumor and adjacent normal colonic tissue using quantitative PCR for mRNA levels. Detection of CTSB protein expression in tissues was carried out using both immunohistochemistry and western blotting techniques. ELISA analysis showed that in sera obtained from CRC patients, the CTSB concentration was significantly higher in late stage patients with lymph node metastases when compared to early stage patients with values of 2.9 and 0.33 ng/ml, respectively (P=0.001). The majority of tumors studied had detectable CTSB protein expression with significant increased positive staining in tumors cells when compared with matched normal colon subjects (P=0.006). The mRNA expression in early stage CRC compared to late stage CRC was 0.04±0.01 and 0.07±0.02, respectively. Increased mRNA expression was more frequently observed in the advanced cancer stages with lymph node metastases when compared with the control (P=0.002). Mann-Whitney test and paired t-test were used to compare serum CTSB and mRNA levels in early and late tumor stage. A subset of four paired tissue extracts were analyzed by western blotting. The result confirmed a consistent increase in the CTSB protein expression level in tumor tissues compared with that noted in the adjacent normal mucosal cells. These findings indicate that CTSB may be an important prognostic biomarker for late stage CRC and cases with lymph node metastases in the Middle Eastern population. Monitoring serum CTSB in CRC patients may predict and/or diagnose cases with lymph node metastases.

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