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Molecular Oncology, Markers, Clinical Correlates |
Subunit As Potential Serum Biomarker in Ovarian Cancer
Laboratory of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women’s Hospital [B. Y., D. W. C., V. P., L. F., R. S. B., S. C. M.], Dana-Farber Cancer Institute, Dana-Farber Harvard Cancer Center [D. W. C., R. S. B., S. C. M.], Biostatistics Center, Massachusetts General Hospital [S. J. S., N. K. H.], and Department of Cell Biology [S. P. G., L. J. L.], Harvard Medical School, Boston, Massachusetts 02115, and University of Texas Southwestern Medical Center, Dallas, Texas 77030 [J. O. S.]
Purpose: The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays.
Experimental Design: Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens.
Results: Using surface enhanced laser desorption and ionization, we found a serum biomarker at 
11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the 
chain of haptoglobin. ELISA indicated that Hp- was 
2-fold higher in cancer serum compared with normal, benign tumor, and other gynecological cancers (P < 0.05) and had 64% sensitivity at 90% specificity alone and 91% sensitivity and 95% specificity if combined with CA125.
Conclusions: Haptoglobin-derived subunit is a potential marker for ovarian cancer that is complementary to CA125. MS-based protein profiling is a valuable tool for screening protein markers and useful to detect post-translational modification of tumor-associated proteins or abnormal metabolic products. However, confirmation of protein identity with specific antibodies is crucial for clinical application and functional studies.
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