Caspase-Cleaved Cytokeratin 18 as a Potential Molecular Biomarker for Monitoring Chemotherapeutic Response in Breast Cancer Patients

Abstract

Background: Breast cancer is one of the most dreadful cancer types, with the highest mortality and morbidity in women in both low and high-income countries. Cytokeratins can be applied as noninvasive, efficient and satisfactory molecular tools to monitor and predict the response to chemotherapy for breast cancer. Objective: This study was intended to explore the potential application of ccCK18 as a molecular biomarker for monitoring and predicting the efficacy of chemotherapy on breast cancer patients. Methodology: A hospital-based prospective study was conducted on 40 breast cancer patients and 38 apparently healthy control individuals in Black Lion Specialized Hospital. Blood samples were obtained from study subjects and control groups before chemotherapy, at 4 and 6 hours after chemotherapy. An ELISA assay was applied to measure plasma caspase-cleaved Cytokeratin 18 (ccCK18). The association between expression of ccCK18 and the tumor metastasis and stages and grades were determined with ELISA. Different biochemical tests were also carried out to investigate the function of liver in relation to ccCK18 level with respect to cancer chemotherapy. Wilcoxon signed rank test, Spearman’s rho test and paired t-test were applied as statistical tools to determine association and correlation among different the study parameters. A p-value of <0.05 was considered as statistically significant. Results: The baseline levels of plasma ccCK-18 were significantly higher in patients with breast cancer than those in the control group (% CI= 95%, p<0.05). The level of ccCK-18 was also significantly increased at 6 hours after chemotherapy (p<0.05). Patients with pT3 tumor size displayed the highest median level compared to other tumor sizes. The ccCK-18 level was observed to be higher among patients with distant metastasis than in nonmetastatic patients. Lactate dehydrogenase (LDH) levels were also elevated at 6 hours, following chemotherapy. Plasma liver function tests (ALT, AST, ALP and total bilirubin) were normal before and after chemotherapy, indicating that there was no major liver damage following chemotherapy. Conclusion: ccCK-18 level in blood could be used as a molecular biomarker for monitoring the disease and predicting the response of patients to breast cancer chemotherapy, particularly in low settings; however, further studies with other protocols are warranted to tailor chemotherapy treatment in a better way.