Ovarian cancer specific kallikrein profile in effusions

OBJECTIVE: Kallikreins belong to the serine protease family and their roles as cancer associated markers have been proposed. However, a comprehensive and parallel analysis of different secreted kallikreins in ovarian cancer has not been performed. This study was undertaken to profile the secreted kallikreins in cancer effusion supernatants. METHODS: We applied ELISA to measure the protein levels of nine kallikreins (4-8, 10, 11, 13, and 14) in a total of 221 effusion supernatants obtained from ovarian cancer, benign non-neoplastic diseases and a variety of other neoplastic diseases. RESULTS: Our results demonstrated that ovarian cancer effusions contained higher levels of all kallikreins analyzed except kallikrein 4, as compared to benign effusions (p<0.0005) and other cancer types (p<0.03). Unsupervised principal component analyses demonstrated a unique cluster of ovarian cancer samples which were distinct from benign effusions and other cancer groups based on measurements of secreted kallikreins 5-8, 10, 11, 13 and 14. Supervised combinations of the eight kallikreins achieved areas under ROC curve of 0.994 and 0.961 in separating ovarian cancer from benign effusion groups and other cancer groups, respectively. Among kallikreins, kallikreins 6, 7, 8, and 10 showed the highest statistical power in distinguishing ovarian cancer from benign controls and other cancer groups and these kallikreins could diagnose false negative cases based on cytology. CONCLUSIONS: The above findings indicate that kallikreins 6, 7, 8 and 10 are the four most specific secreted kallikreins in ovarian cancer. These kallikreins may have clinical implications in the differential diagnosis of ovarian carcinoma from benign diseases and other cancer types.