A Selected Reaction Monitoring Approach for Validating Candidate Biomarkers

ABSTRACT: We here describe a Selected Reaction Monitoring (SRM)-based approach for the discovery and validation of peptide biomarkers for cancer. The first stage of this approach is the direct identification of candidate peptides through comparison of proteolytic peptides derived from the plasma of cancer patients or healthy individuals. Several hundred candidate peptides were identified through this method, providing challenges for choosing and validating the small number of peptides that might prove diagnostically useful. To accomplish this validation, we used two-dimensional chromatography coupled with Selected Reaction Monitoring of candidate peptides. We applied this approach, called SAFE-SRM (for Sequential Analysis of Fractionated Eluates by Selected Reaction Monitoring) to plasma from cancer patients and discovered two peptides encoded by the PPIA (peptidyl-prolyl cis-trans isomerase A) gene whose abundance was increased in the plasma of ovarian cancer patients. At optimal thresholds, elevated levels of at least one of these two peptides was detected in 43 (68.3%) of 63 women with ovarian cancer but in none of 50 healthy controls. In addition to providing a potentially new biomarker for ovarian cancer, this approach is generally applicable to the discovery of proteins and peptides characteristic of various disease states.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: QING WANG  

LAB HEAD: Qing Wang

PROVIDER: PXD008094 | Pride | 2017-12-11

REPOSITORIES: Pride