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[Cancer Research 64, 5882-5890, August 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Three Biomarkers Identified from Serum Proteomic Analysis for the Detection of Early Stage Ovarian Cancer

Zhen Zhang1, Robert C. Bast, Jr.2, Yinhua Yu2, Jinong Li1, Lori J. Sokoll1, Alex J. Rai1, Jason M. Rosenzweig1, Bonnie Cameron1, Young Y. Wang1, Xiao-Ying Meng3, Andrew Berchuck4, Carolien van Haaften-Day5, Neville F. Hacker5, Henk W. A. de Bruijn6, Ate G. J. van der Zee6, Ian J. Jacobs7, Eric T. Fung3 and Daniel W. Chan1

1 Department of Pathology, Biomarker Discovery Center, Johns Hopkins Medical Institutions, Baltimore, Maryland; 2 M. D. Anderson Cancer Center, Houston, Texas; 3 Ciphergen Biosystems, Inc., Fremont, California; 4 Duke University Medical Center, Durham, North Carolina; 5 The Royal Hospital for Women, Randwick, New South Wales, Australia; 6 University Hospital Groningen, Groningen, the Netherlands; and 7 Bart’s and The London, Queen Mary’s School of Medicine, London, United Kingdom

Early detection remains the most promising approach to improve long-term survival of patients with ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive epithelial ovarian cancer, 42 with other ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential biomarkers. The results were validated using the samples from two of the remaining centers. After protein identification, biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with ovarian cancer, and 20 each with breast, colon, and prostate cancers. Three biomarkers were identified as follows: (a) apolipoprotein A1 (down-regulated in cancer); (b) a truncated form of transthyretin (down-regulated); and (c) a cleavage fragment of inter-{alpha}-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three biomarkers and CA125 [74% (95% CI, 52–90%)] was higher than that of CA125 alone [65% (95% CI, 43–84%)] at a matched specificity of 97% (95% CI, 89–100%). When compared at a fixed sensitivity of 83% (95% CI, 61–95%), the specificity of the model [94% (95% CI, 85–98%)] was significantly better than that of CA125 alone [52% (95% CI, 39–65%)]. These biomarkers demonstrated the potential to improve the detection of early stage ovarian cancer.




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