Proteomic tracking of serum protein isoforms as screening biomarkers of ovarian cancer

Nuzhat Ahmed, Karen T Oliva, Gillian Barker, Peter Hoffmann, Shane Bernadine Reeve, Alexander Ian Smith, Michael A Quinn, Greg E Rice

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Abstract

Epithelial ovarian cancer is the fourth leading cause of cancer death among women. Due to the asymptomatic nature and poor survival characteristic of the disease, screening for specific biomarkers for ovarian cancer is a major health priority. Differentially expressed proteins in the serum of ovarian cancer patients have the potential to be used as cancer-specific biomarkers. In this study, proteomic methods were used to screen 24 serum samples from women with high-grade ovarian cancer and compared to a control group of 11 healthy women. Affigel-Blue treated serum samples were processed either by linear (pH 4-7) or narrow range (pH 5.5-6.7) IEF strips for the first dimension. Proteins separated in first dimension were resolved by 8-16 gradient SDS-PAGE. Protein spots were visualized by SYPRO Ruby staining, imaged by FX-imager and compared and analyzed by PDQuest software. Twenty-two protein spots were consistently differentially expressed between normal and ovarian cancer patients by resolving proteins in a linear pH strip of 4-7 for the first dimension. Six of the protein spots, significantly up-regulated in grade 3 ovarian cancer patients (p <0.05), were identified by MALDI-TOF MS and Western blotting as the isoforms of haptoglobin precursor. When serum proteins were resolved on narrow pH range strips (5.5-6.7), 23 spots were consistently differentially expressed between normal and grade 3 ovarian cancer patients. Of these, 4 protein spots significantly down regulated in grade 3 ovarian cancer patients (p <0.05) were identified by MALDI-TOF MS and Western blotting, as isoforms of transferrin precursor. Increased expression of serum haptoglobin and transferrin was also identified in peritoneal tumor fluid obtained from women diagnosed with grade 2/3 ovarian cancer (n = 7). Changes in the expression of haptoglobin and transferrin in the serum of .......
Original languageEnglish
Pages (from-to)4625 - 4636
Number of pages12
JournalProteomics
Volume5
Issue number17
DOIs
Publication statusPublished - 2005

Cite this

Ahmed, N., Oliva, K. T., Barker, G., Hoffmann, P., Reeve, S. B., Smith, A. I., Quinn, M. A., & Rice, G. E. (2005). Proteomic tracking of serum protein isoforms as screening biomarkers of ovarian cancer. Proteomics, 5(17), 4625 - 4636. https://doi.org/10.1002/pmic.200401321