Epithelial ovarian cancer biomarker

ABSTRACT: Protein biomarkers of early stages of disease are critical for managing the disease and improving outcomes. Unfortunately, discovery of protein biomarkers is hampered by the limited availability of assays for sensitive and reproducible quantification of proteins in complex biological matrices such as blood plasma. In the recent years, Selected Reaction Monitoring (SRM) has emerged as a robust mass spectrometric method, capable of overcoming this limitation. Here, we present a comprehensive SRM-based strategy for developing protein biomarkers for epithelial ovarian cancer, and illustrate the extent to which SRM platform, combined with sound experimental design and statistical analysis, results in robust detection of predictive analytes. First, the biomarker development was guided by a discovery-driven proteomic effort to detect potential N-glycoprotein biomarker candidates in tissue of a genetically stable ovarian cancer mouse model. Next, 65 candidate markers were reproducibly quantified with SRM assays across a large cohort of over 200 plasma samples from ovarian cancer patients and healthy controls. Finally, these measurements were used to derive 5-protein signatures for distinguishing individuals with epithelial ovarian cancer from healthy controls. The sensitivity of the candidate biomarker signature in combination with CA125 ELISA-based measurements currently used in clinic, exceeded that of CA125 ELISA-based measurements alone. The SRM-based strategy in this study is broadly applicable. It can be used in any study that requires accurate and reproducible quantification of selected proteins in a high-throughput and multiplexed fashion.

INSTRUMENT(S): 4000 QTRAP, QTRAP 5500, TSQ Vantage

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Ruth Huttenhain   Meena Choi  

PROVIDER: MSV000084048 | MassIVE | Tue Jul 02 10:49:00 BST 2019

SECONDARY ACCESSION(S): PXD015303

REPOSITORIES: MassIVE