Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Proteomic Tissue Biomarkers for Early Prediction of Prostate Cancer Progression (#143)

Sudhir Srivastava 1 , Jacob Kagan 1
  1. Cancer Biomarkers Research Group, National Cancer Institute, National Institutes of Health, GAITHERSBURG, MARYLAND, United States

Although approximately 40% of the screen-detected prostate cancers are indolent, advanced-stage prostate cancer is a lethal disease with 5-year survival rates around 29%. The challenge is to identify biomarkers for early detection of aggressive disease, when the cancer is still organ-confined. We have developed ultra-sensitive, high-pressure, high-resolution separations coupled with intelligent selection and multiplexing-selected reaction monitoring (PRISM-SRM) assays for 52 protein markers selected from existing prostate cancer genomics data sets and known prostate cancer drivers. These PRISM-SRM assays were applied in analysis of organ-confined primary tumors from prostate cancer patients (n = 338) presenting different post-surgery features: distant metastasis, biochemical recurrence (BCR), and no progression after more than ten years of follow-up after radical prostatectomy. Several prostate differentiation/androgen receptor signaling related proteins (FOLH1, PSA and NCOA) and tumor progression-related proteins (TGFB1, CCND1 and SPARC) had significantly different expression levels between the three groups. Combining the protein biomarker panel with existing clinical based models achieved an area under the receiver operating characteristic curve (AUC) of 0.88 and a negative predictive value (NPV) of 0.91 for predicting distant metastasis. The molecular test of these protein biomarkers therefore provides a complementary tool for early detection of aggressive prostate cancer, as well as better selection of patients with indolent and low-risk cancers for active surveillance.