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Biomark Insights. 2017 Jun 5;12:1177271917710948. doi: 10.1177/1177271917710948. eCollection 2017.

Data-Independent Acquisition and Parallel Reaction Monitoring Mass Spectrometry Identification of Serum Biomarkers for Ovarian Cancer.

Author information

1
W.M. Keck Foundation Biotechnology Resource Laboratory, Yale School of Medicine, Yale University, New Haven, CT, USA.
2
Yale Mass Spectrometry & Proteomics Resource, Yale School of Medicine, Yale University, New Haven, CT, USA.
3
Department of Molecular Biophysics and Biochemistry, Yale School of Medicine, Yale University, New Haven, CT, USA.
4
Biostatistics Department, School of Public Health, Yale University, New Haven, CT, USA.
5
Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, Yale University, New Haven, CT, USA.

Abstract

A data-independent acquisition (DIA)/parallel reaction monitoring (PRM) workflow was implemented to identify improved ovarian cancer biomarkers. Data-independent acquisition on ovarian cancer versus control sera and literature searches identified 50 biomarkers and indicated that apolipoprotein A-IV (ApoA-IV) is the most significantly differentially regulated protein. Parallel reaction monitoring with Targeted Ovarian Cancer Proteome Assay validated differential ApoA-IV expression and quantified 9 other biomarkers. Random Forest (RF) analyses achieved 92.3% classification accuracy and confirmed ApoA-IV as the leading biomarker. Indeed, all samples were classified correctly with an [ApoA-IV] breakpoint. The next best biomarkers were C-reactive protein, transferrin, and transthyretin. The Targeted Ovarian Cancer Proteome Assay suggests that ApoA-IV is a more reliable biomarker than had been determined by immunological assays and it is a better biomarker than ApoA-I, which is in the OVA1 test for ovarian cancer. This research provides a PRM/RF approach together with 4 promising biomarkers to speed the development of a clinical assay for ovarian cancer.

KEYWORDS:

Data-independent acquisition; ovarian cancer; parallel reaction monitoring; serum biomarkers; targeted proteomics

Conflict of interest statement

DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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