Prognostic value and characterization of the ovarian cancer-specific antigen CA166-9

COC166-9 is an ovarian cancer-specific monoclonal antibody, and COC166-9-based immunotherapy has been shown to possess killing effects against ovarian cancer cells in vitro and in vivo. However the antigen recognized by COC166-9 (COC166-9-Ag, CA166-9) has not been identified and the clinical significance of CA166-9 expression remains unknown. We found that CA166-9 was positive in 53.1% of ovarian cancer tissues. Expression of CA166-9 was strongly correlated with the cancer recurrence (P<0.001). Patients with positive CA166-9 had substantially shorter overall survival (P=0.026) and disease-free survival (P=0.002). CA166-9 was also shown to be an independent predictive factor for overall survival (HR=2.454, P=0.016) and disease-free survival (HR=2.331, P=0.021). We identified CA166-9 as human immunoglobulin γ-1 heavy chain constant region (IGHG1). Purified IGHG1 promoted proliferation, migration, and invasion of CA166-9-negative ovarian cancer HOC1A cells, whereas it had minimal effects on the phenotypes of CA166-9-positive ovarian cancer CAOV-3 cells. In addition, overexpression of IGHG1 enhanced migration of ovarian cancer cells. On the contrary, COC166-9 inhibited proliferation, migration, and invasion of CAOV-3 cells, but had no effects on HOC1A cells. Therefore, IGHG1 similarly to CA166-9, could play an important role in ovarian cancer development and may serve as a potential prognostic marker and a therapeutical target for ovarian cancer.