MassIVE MSV000080202

Partial Public

Data-Independent Acquisition (DIA) and Parallel Reaction Monitoring (PRM) Mass Spectrometry Identification of Serum Biomarkers for Ovarian Cancer

Description

Purpose: Since >70% of ovarian cancer diagnoses are made after it is too late for successful treatment, a Data Independent Acquisition (DIA) and Parallel Reaction Monitoring (PRM) mass spectrometry workflow was implemented to identify improved biomarkers in sera. Experimental Design: DIA analyses of seven ovarian cancer and seven control sera and literature searches identified 50 biomarkers. PRM analyses with the Targeted Ovarian Cancer Proteome Assay (TOCPA) validated differential expression of 10 biomarkers, with Random Forest (RF) analyses evaluating their ability to classify the 14 samples. Results: The leading biomarker was Apolipoprotein A-IV (ApoA-IV) which was reduced by ~60% in ovarian cancer. All samples could be classified correctly with a breakpoint at ~54.4% of the average control [ApoA-IV]. The next most reliable biomarkers were C-reactive protein and transthyretin. Conclusions and clinical relevance: A DIA/TOCPA PRM workflow was developed for identifying and validating ovarian cancer biomarkers. TOCPA demonstrated that ApoA-IV is a more reliable biomarker than had been determined by immunological assays. Indeed, ApoA-IV is a better biomarker than ApoA-I, which is in the OVA1 test for detecting ovarian cancer in pelvic masses. This research represents an important step towards improving the OVA1 test and developing a clinical test for ovarian cancer. [dataset license: CC0 1.0 Universal (CC0 1.0)]

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

Contact

Principal Investigators:
(in alphabetical order)
Kenneth R. Williams
Submitting User: KRWilliams
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