Discovery and Longitudinal Evaluation of Candidate Protein Biomarkers for Disease Recurrence in Prostate Cancer

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• 作者：Claire L. Tonry ; Darren Doherty ; Carmel O鈥橲hea ; Brian Morrissey ; Lisa Staunton ; Brian Flatley ; Aoife Shannon ; John Armstrong ; Stephen R. Pennington
• 刊名：Journal of Proteome Research
• 出版年：2015
• 出版时间：July 2, 2015
• 年：2015
• 卷：14
• 期：7
• 页码：2769-2783
• 全文大小：1120K
• ISSN：1535-3907

文摘

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鈥揗S/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.