Advances in Brief Haptoglobin- Subunit As Potential Serum Biomarker in Ovarian Cancer: Identification and Characterization Using Proteomic Profiling and Mass Spectrometry

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 Hpwas <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.