Deciphering the peptidome of urine from ovarian cancer patients and healthy controls

Clinical Proteomics

Christopher R Smith²  Julia Ridley⁵  Vathany Kulasingam³  Hari Kosanam⁴  Felix Leung⁸  Eleftherios P Diamandis⁶  Marcus Q Bernardini⁷  Ihor Batruch⁴  Josep Miquel Bauça¹ 

[1] Servei d’Anàlisis Clíniques, Hospital Universitari Son Espases, Palma de Mallorca, SpainServei d’Anàlisis Clíniques, Hospital Universitari Son Espases, Palma de Mallorca, SpainServei d’Anàlisis Clíniques, Hospital Universitari Son Espases, Palma de Mallorca, Spain;Department of Clinical Biochemistry, University Health Network, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada;Department 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 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 Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;Samuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada;Department of Psychosocial Oncology and Palliative Care, Princess Margaret Cancer Center, University Health Network, Toronto, CanadaDivision of Palliative Care, Department of Community and Palliative Medicine, University of Toronto, Toronto, CanadaDepartment of Psychosocial Oncology and Palliative Care, Princess Margaret Cancer Center, University Health Network, Toronto, CanadaDepartment of Psychosocial Oncology and Palliative Care, Princess Margaret Cancer Center, University Health Network, Toronto, CanadaDivision of Palliative Care, Department of Community and Palliative Medicine, University of Toronto, Toronto, CanadaDivision of Palliative Care, Department of Community and Palliative Medicine, University of Toronto, Toronto, CanadaDepartment of Psychosocial Oncology and Palliative Care, Princess Margaret Cancer Center, University Health Network, Toronto, CanadaDivision of Palliative Care, Department of Community and Palliative Medicine, University of Toronto, Toronto, Canada;Department of Clinical Biochemistry, University Health Network, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 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, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Clinical Biochemistry, University Health Network, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, 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, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada;Department of Obstetrics and Gynecology, University of Toronto, Toronto, CanadaDepartment of Obstetrics and Gynecology, University of Toronto, Toronto, CanadaDepartment of Obstetrics and Gynecology, University of Toronto, Toronto, Canada;Samuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, CanadaSamuel Lunenfeld Research Institute, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

关键词: Biomarker;    Early diagnosis;    Mass spectrometry;    Ovarian cancer;    Urine peptidome;   

DOI  :  10.1186/1559-0275-11-23

来源: Humana Press Inc

【 摘 要 】

Abstract

Background

Ovarian cancer (OvCa) is the most lethal gynecological malignancy. The emergence of high-throughput technologies, such as mass spectrometry, has allowed for a paradigm shift in the way we search for novel biomarkers. Urine-based peptidomic profiling is a novel approach that may result in the discovery of noninvasive biomarkers for diagnosing patients with OvCa. In this study, the peptidome of urine from 6 ovarian cancer patients and 6 healthy controls was deciphered.

Results

Urine samples underwent ultrafiltration and the filtrate was subjected to solid phase extraction, followed by fractionation using strong cation exchange chromatography. These fractions were analyzed using an Orbitrap mass spectrometer. Over 4600 unique endogenous urine peptides arising from 713 proteins were catalogued, representing the largest urine peptidome reported to date. Each specimen was processed in triplicate and reproducibility at the protein (69-76%) and peptide (58-63%) levels were noted. More importantly, over 3100 unique peptides were detected solely in OvCa specimens. One such promising biomarker was leucine-rich alpha-2-glycoprotein (LRG1), where multiple peptides were found in all urines from OvCa patients, but only one peptide was found in one healthy control urine sample.

Conclusions

Mining the urine peptidome may yield highly promising novel OvCa biomarkers.

【 授权许可】

Unknown