TY - JOUR
T1 - Prostate Cancer Diagnosis in the Clinic Using an 8-Protein Biomarker Panel
AU - Jones, Abby L.
AU - Dhanapala, Lasangi
AU - Baldo, Thaísa A.
AU - Sharafeldin, Mohamed
AU - Krause, Colleen E.
AU - Shen, Min
AU - Moghaddam, Shirin
AU - Faria, Ronaldo C.
AU - Dey, Dipak K.
AU - Watson, R. William
AU - Andrawis, Ramez
AU - Lee, Norman H.
AU - Rusling, James F.
N1 - Publisher Copyright:
© 2020 American Chemical Society.
PY - 2021/1/19
Y1 - 2021/1/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097758429&partnerID=8YFLogxK
U2 - 10.1021/acs.analchem.0c04034
DO - 10.1021/acs.analchem.0c04034
M3 - Article
AN - SCOPUS:85097758429
SN - 0003-2700
VL - 93
SP - 1059
EP - 1067
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 2
ER -