Thymidine kinase activity as a prognostic tool in blood samples of primary ovarian cancer patients.

Abstract

e17602 Background: Prognostic markers in serous ovarian cancer (OC) include CA125 serum level, FIGO-stage, lymph node-status, postoperative residual tumor, amount of intraoperative ascites and response to platinum-based therapy. However, easily accessible prognostic biomarkers are missing. One candidate might be thymidine kinase 1 activity (TKa), expressed as a cell transverse through the cell cycle with high activity in proliferating cells. We determined TKa before and after adjuvant chemotherapy in a representative group of primary serous OC patients to elucidate its prognostic value. Methods: Blood was drawn from a representative cohort of 245 OC patients at first diagnosis, before starting primary cyto-reductive surgery (baseline) and after therapy (n=44) to study TKa in serum and plasma. Samples were analyzed blinded using the DiviTum TKa assay, a clinically and analytically validated, CE marked and FDA approved ELISA. Cut-off finding was done analogue to overall survival (OS), the point with the most significant (log-rank test) split. Statistical analysis was conducted via log-rank test and univariate or multivariate Cox regression. Results: Median TKa in serum samples was 157 DuA (min/max 39/1911 DuA) resulting in a cut-off of 85 DuA at baseline to calculate correlations with OS and 151 DuA for disease free survival (DFS), respectively. TKa measurements in plasma samples showed a median value of 165 DuA (min/max 39/1585 DuA) resulting in the cut-off 235 DuA for OS and 123 DuA for DFS. High TKa serum levels significantly correlated with shorter DFS (p=0.027) as well as OS (p=0.002). TKa in plasma showed the same correlation with decreased DFS (p=0.002) and OS (p<0.001) [shown in Fig.1]. Multivariate Cox regression analysis confirmed TKa as an independent prognostic marker for OS in plasma samples. Furthermore, high TKa at baseline correlated significantly with higher FIGO stage, postoperative residual tumor and predicted platinum resistance. Conclusions: Baseline TKa levels in both serum and plasma significantly correlated with OS and DFS, which identifies circulating TKa as a promising prognostic marker in OC. It might further serve as a predictive marker for response to platinum-based chemotherapy, however, prospective validation of these results is needed in order to further specify the clinical value of TKa.