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

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Jones, Abby L. ^[1] ; Dhanapala, Lasangi ^[1] ; Baldo, Thaisa A. ^[2] ; Sharafeldin, Mohamed ^[1] ; Krause, Colleen E. ^[3] ; Shen, Min ^[1] ; Moghaddam, Shirin ^[4] ; Faria, Ronaldo C. ^[2] ; Dey, Dipak K. ^[5] ; Watson, R. William ^{[6, 7]} ; Andrawis, Ramez ^[8] ; Lee, Norman H. ^{[9, 10]} ; Rusling, James F. ^{[11, 1, 12, 13]}

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^[1] Univ Connecticut, Dept Chem, Storrs, CT 06269 - USA

^[2] Univ Fed Sao Carlos, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Hartford, Dept Chem, Hartford, CT 06117 - USA

^[4] Univ Coll Cork, Sch Math Sci, Cork T12 YT20 - Ireland

^[5] Univ Connecticut, Dept Stat, Storrs, CT 06269 - USA

^[6] Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4 - Ireland

^[7] Univ Coll Dublin, UCD Sch Med & Med Sci, Dublin 4 - Ireland

^[8] George Washington Univ, Dept Urol, Washington, DC 20037 - USA

^[9] George Washington Univ, Dept Pharmacol & Physiol, Washington, DC 20037 - USA

^[10] GW Canc Ctr, Washington, DC 20052 - USA

^[11] Univ Connecticut, Inst Mat Sci, Storrs, CT 06269 - USA

^[12] Natl Univ Ireland Galway, Sch Chem, Galway H91 CF50 - Ireland

^[13] UConn Hlth Ctr, Dept Surg, Farmington, CT 06232 - USA

• Tipo de documento: Artigo Científico
• Fonte: Analytical Chemistry; v. 93, n. 2, p. 1059-1067, JAN 19 2021.
• Citações Web of Science: 0

Resumo

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 similar to 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 mu L 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. (AU)

• Processo FAPESP: 17/24053-7 - Desenvolvimentos de métodos eletroquímicos simples para a detecção de biomarcadores visando o diagnóstico de doenças
• Beneficiário: Ronaldo Censi Faria
• Modalidade de apoio: Auxílio à Pesquisa - Regular