Characterization of novel monoclonal antibodies that target proteins differentially expressed in hepatocellular carcinoma : a proteomics approach

Abstract

Hepatocellular carcinoma (HCC) is the sixth common cancer in the world. Because of the late diagnosis of the disease, survival rates are still poor in the HCC patients. Surveillance strategies have to be developed in populations with high risk groups having premalignant diseases for HCC, such as liver cirrhosis. The usage of serum and histology-based biomarkers assists health professionals to evaluate the patients. Despite of the advances in diagnostic methods, there is still a need to develop novel biomarkers for early detection of HCC. Therefore, we aimed to develop new biomarkers with higher sensitivity and specificity for HCC to improve the surveillance of the patients. Using an apoptotic HCC cell line, HUH7, and SIP1 proteins, we generated novel monoclonal antibodies (mAbs). 6D5, 1C6 and 6E5 hybridoma clones were chosen for characterization studies because of their strong reactivity in cell-ELISA assays. We found differential reactivity pattern for those novel mAbs in a panel of human sections consisting of tumors, benign liver diseases, normal tissues and a variety of cell lines. Using proteomics methods, we identified candidate target proteins for the 6D5 mAb. Better characterization of these target proteins will provide a better understanding of the molecular pathways in the HCC and aid in the research for developing newer therapeutic agents. In conclusion, our candidate biomarker mAbs can be used in the early diagnosis of HCC as well as in drug development studies.