title: Discovery and Longitudinal Evaluation of Candidate Protein Biomarkers for Disease Recurrence in Prostate Cancer.
abstract: When compared with hormonal therapy alone, treatment with combined hormone and radiation therapy (CHRT) gives improved disease-specific survival outcomes for patients with prostate cancer; however, a significant number of CHRT patients still succumb to recurrent disease. The purpose of this study was to use longitudinal patient samples obtained as part of an ongoing noninterventional clinical trial (ICORG06-15) to identify and evaluate a potential serum protein signature of disease recurrence. Label-free LC-MS/MS based protein discovery was undertaken on depleted serum samples from CHRT patients who showed evidence of disease recurrence (n = 3) and time-matched patient controls (n = 3). A total of 104 proteins showed a significant change between these two groups. Multiple reaction monitoring (MRM) assays were designed for a subset of these proteins as part of a panel of putative prostate cancer biomarkers (41 proteins) for evaluation in longitudinal serum samples. These data revealed significant interpatient variability in individual protein expression between time of diagnosis, disease recurrence, and beyond and serve to highlight the importance of longitudinal patient samples for evaluating the use of candidate protein biomarkers in disease monitoring.
authors.affiliation: †Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Dublin, Ireland.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Tonry
authors.affiliation: †Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Dublin, Ireland.
authors.forename: Darren
authors.initials: D
authors.lastname: Doherty
authors.affiliation: ‡St. Luke's Hospital, Rathgar, Dublin 6, Dublin, Ireland.
authors.forename: Carmel
authors.initials: C
authors.lastname: O'Shea
authors.affiliation: †Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Dublin, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Morrissey
authors.affiliation: †Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Dublin, Ireland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Staunton
authors.affiliation: †Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Dublin, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Flatley
authors.affiliation: ‡St. Luke's Hospital, Rathgar, Dublin 6, Dublin, Ireland.
authors.forename: Aoife
authors.initials: A
authors.lastname: Shannon
authors.affiliation: ‡St. Luke's Hospital, Rathgar, Dublin 6, Dublin, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Armstrong
authors.affiliation: †Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Dublin, Ireland.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pennington
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002853:Chromatography, Liquid; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D011471:Prostatic Neoplasms / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
keywords: LC−MS/MS; MRM; biomarkers; longitudinal evaluation; prostate cancer; serum