Deciphering the ovarian cancer ascites fluid peptidome

Clinical Proteomics

Christopher R Smith²  Vathany Kulasingam¹  Anand Bery¹  Felix Leung³  Eleftherios P Diamandis⁴ 

[1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, Canada;Department of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada

关键词: Biomarker;    Early diagnosis;    Mass spectrometry;    Ovarian cancer;    Ascites fluid;    Peptidome;   

DOI  :  10.1186/1559-0275-11-13

来源: Humana Press Inc

【 摘 要 】

Abstract

Background

Conventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis).

Results

Following ultrafiltration of the ascites fluids to remove larger proteins, each filtrate was subjected to solid phase extraction and fractionated using strong cation exchange chromatography. The resultant fractions were analyzed using an Orbitrap mass spectrometer. We identified over 2000 unique endogenous peptides derived from 259 proteins. We then catalogued over 777 peptides that were found only in ovarian cancer ascites. Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.

Conclusions

Peptidomics may uncover previously undiscovered disease-specific endogenous peptides that warrant further investigation as biomarkers for ovarian cancer.

【 授权许可】

Unknown