Plasma concentrations of the vitamin E-binding protein afamin are associated with overall and progression-free survival and platinum sensitivity in serous ovarian cancer--a study by the OVCAD consortium.

ABSTRACT

OBJECTIVE: Comparative proteomics identified the plasma protein afamin as potential biomarker for ovarian cancer (OC). Significantly decreased afamin plasma concentrations in pre-therapeutic OC patients reconstituted to control values after successful tumor surgery. This study evaluates the association of afamin with survival and response to therapy in serous OC patients within the OVCAD consortium project. METHODS: We measured afamin in 215 pre-therapeutic plasma samples, 246 tumor lysates and 109 plasma samples taken 6months after finishing platinum-based chemotherapy. Differences in afamin plasma concentrations among FIGO stages were tested by Kruskal-Wallis test; association of afamin concentrations with overall and progression-free survival was evaluated using Kaplan-Meier survival plots and multivariate adjusted COX regression analysis. RESULTS: Pre-therapeutic afamin correlated significantly with FIGO stages (p=0.012) and was lower in the presence of metastases (p=0.013) and poorly differentiated OC in patients responding to therapy (p=0.016). Afamin ≥48.0mg/L was also associated with a lower hazard ratio for recurrent disease as compared to afamin <48.0mg/L (p=0.007). Post-therapeutic afamin ≥48mg/L was positively correlated with overall (p<0.001) and progression-free (p=0.012) survival and was lower in non-responders than in responders (p=0.048). Thus, afamin returned post-therapeutically to values of healthy controls in responders (p<0.001) but not in non-responders (p=0.114). Afamin in tumor lysates was lower in poorly differentiated OC than in G 1+2 tumors (p=0.041). Higher afamin concentrations in tumor lysates were associated with increased overall survival (p=0.003). CONCLUSION: These data indicate that afamin is associated with therapy response and survival rate in advanced OC patients.