Abstract 2573: Selection of candidate biomarkers for aggressive prostate cancer based on targeted proteomics

Abstract

Abstract Mass spectrometry based targeted proteomics such as selected reaction monitoring (SRM) provides an effective, antibody-independent strategy for sensitive, specific and multiplexed verification of genomics biomarker candidates at the protein level. In order to identify a panel of proteins with the potential to predict prostate cancer progression, we have selected 52 protein candidates from existing prostate cancer genomics data sets and validated cancer drivers, and performed quantitative proteomics analysis in tissue samples using the highly sensitive PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing)-SRM approach. PRISM-SRM assays have been developed for the 52 prostate cancer biomarker candidates including: prostate cancer relevant genes and common cancer drivers. One set of 105 formalin-fixed paraffin-embedded (FFPE) whole mount prostate tissue specimens were analyzed using PRISM-SRM with heavy isotope-labeled synthetic peptides as internal standards: 20 primary tumors from patients showing metastatic progression, 37 primary tumors from patients who showed biochemical recurrence (BCR), and 48 primary tumors from patients with no BCR or metastatic progression after more than ten years of follow-up after radical prostatectomy. Overall, PRISM-SRM analyses of the FFPE tissue samples enabled the detection of 42 out of 52 biomarker candidates; in comparison regular LC-SRM without the front-end chromatographic enrichment could detect only 21 of these candidates at the protein level. Kruskal-Wallis test of the PRISM-SRM results provided a statistical evaluation of comparison of relative protein levels among the “no progression”, BCR and “metastatic progression” groups. Prostate differentiation/AR signaling related proteins (FOLH1, PSA and NCOA) or tumor progression (TGFB1, CCND1 and SPRC) were significantly different between the three groups. These promising biomarker candidates for early detection of aggressive prostate cancer are being further evaluated, individually and in panels, in an independent cohort of 234 samples for their potential prognostic applications. In summary, PRISM-SRM provides a highly sensitive method for quantification and rapid screening of promising cancer biomarker candidates defined by multiomics platforms. Citation Format: Yuqian Gao, Hui Wang, Jennifer Cullen, Yongmei Chen, Athena Schepmoes, Gyorgy Petrovics, Thomas Fillmore, Tujin Shi, Wei-Jun Qian, Richard Smith, Sudhir Srivastava, Jacob Kagan, Albert Dobi, Karin Rodland, Shiv Srivastava, Tao Liu. Selection of candidate biomarkers for aggressive prostate cancer based on targeted proteomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2573.