1. ¹Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G1L5, Canada
2. ²Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON M5G1X5, Canada
3. ³Fred Hutchinson Cancer Research Center, Public Health Sciences Division, Seattle, WA 98109, USA
4. ⁴diaDexus Inc., 343 Oyster Point Blvd., South San Francisco, CA 94080, USA
5. ⁵Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno 656 53, Czech Republic

Correspondence: Dr EP Diamandis, Mount Sinai Hospital, Department of Pathology and Laboratory Medicine, 60 Murray Street, 6th Floor, Room L6-201; Toronto Ontario, Canada M5T 3L9; E-mail: ediamandis@mtsinai.on.ca

Received 14 February 2008; Revised 12 June 2008; Accepted 4 August 2008; Published online 2 September 2008.

Abstract

Currently, there are no effective biomarkers for ovarian cancer prognosis or prediction of therapeutic response. The objective of this study was to examine a panel of 10 serum biochemical parameters for their ability to predict response to chemotherapy, progression and survival of ovarian cancer patients. Sera from ovarian cancer patients were collected prior and during chemotherapy and were analysed by enzyme-linked immunosorbent assay for CA125, kallikreins 5, 6, 7, 8, 10 and 11, B7-H4, regenerating protein IV and Spondin-2. The odds ratio and hazard ratio and their 95% confidence interval (95% CI) were calculated. Time-dependent receiver-operating characteristic (ROC) curves were utilised to evaluate the prognostic performance of the biomarkers. The levels of several markers at baseline (c₀), or after the first chemotherapy cycle (rc₁), predicted chemotherapy response and overall or progression-free survival in univariate analysis. A multiparametric model (c₀ of CA125, KLK5, KLK7 and rc₁ of CA125) provided predictive accuracy with area under the ROC curve (AUC) of 0.82 (0.62 after correction for overfitting). Another marker combination (c₀ of KLK7, KLK10, B7-H4, Spondin-2) was useful in predicting short-term (1-year) survival with an AUC of 0.89 (0.74 after correction for overfitting). All markers examined, except KLK7 and regenerating protein IV, were powerful predictors of time to progression (TTP) among chemotherapy responders. Individual and panels of biomarkers from the kallikrein family (and other families) can predict response to chemotherapy, overall survival, short-term (1-year) survival, progression-free survival and TTP of ovarian cancer patients treated with chemotherapy.