Prostate Cancer Diagnosis in the Clinic Using an 8‑Protein Biomarker Panel

• Published in: Analytical chemistry (Washington) Vol. 93; no. 2; pp. 1059 - 1067
• Main Authors: Jones, Abby L, Dhanapala, Lasangi, Baldo, Thaísa A, Sharafeldin, Mohamed, Krause, Colleen E, Shen, Min, Moghaddam, Shirin, Faria, Ronaldo C, Dey, Dipak K, Watson, R. William, Andrawis, Ramez, Lee, Norman H, Rusling, James F
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.01.2021
• Subjects: Antigens; Biomarkers; Biomarkers, Tumor - blood; Biopsy; Blood; Chemistry; Growth factors; Horseradish peroxidase; Humans; Immunoassay; Insulin; Insulin-like growth factor I; Male; Microfluidic Analytical Techniques; Microfluidics; Monocytes; Neoplasm Proteins - blood; Optimization; Patients; Peroxidase; Prostate cancer; Prostatic Neoplasms - blood; Prostatic Neoplasms - diagnosis; Proteins; Quality; Quality of life; Rectum; Regression analysis; Surgery; Tumors
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.0c04034

The inability to distinguish aggressive from indolent prostate cancer is a longstanding clinical problem. Prostate specific antigen (PSA) tests and digital rectal exams cannot differentiate these forms. Because only ∼10% of diagnosed prostate cancer cases are aggressive, existing practice often results in overtreatment including unnecessary surgeries that degrade patients’ quality of life. Here, we describe a fast microfluidic immunoarray optimized to determine 8-proteins simultaneously in 5 μL of blood serum for prostate cancer diagnostics. Using polymeric horseradish peroxidase (poly-HRP, 400 HRPs) labels to provide large signal amplification and limits of detection in the sub-fg mL–1 range, a protocol was devised for the optimization of the fast, accurate assays of 100-fold diluted serum samples. Analysis of 130 prostate cancer patient serum samples revealed that some members of the protein panel can distinguish aggressive from indolent cancers. Logistic regression was used to identify a subset of the panel, combining biomarker proteins ETS-related gene protein (ERG), insulin-like growth factor-1 (IGF-1), pigment epithelial-derived factor (PEDF), and serum monocyte differentiation antigen (CD-14) to predict whether a given patient should be referred for biopsy, which gave a much better predictive accuracy than PSA alone. This represents the first prostate cancer blood test that can predict which patients will have a high biopsy Gleason score, a standard pathology score used to grade tumors.