Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood Journal Article


Authors: Modlin, I. M.; Kidd, M.; Drozdov, I. A.; Boegemann, M.; Bodei, L.; Kunikowska, J.; Malczewska, A.; Bernemann, C.; Koduru, S. V.; Rahbar, K.
Article Title: Development of a multigenomic liquid biopsy (PROSTest) for prostate cancer in whole blood
Abstract: Introduction: We describe the development of a molecular assay from publicly available tumor tissue mRNA databases using machine learning and present preliminary evidence of functionality as a diagnostic and monitoring tool for prostate cancer (PCa) in whole blood. Materials and Methods: We assessed 1055 PCas (public microarray data sets) to identify putative mRNA biomarkers. Specificity was confirmed against 32 different solid and hematological cancers from The Cancer Genome Atlas (n = 10,990). This defined a 27-gene panel which was validated by qPCR in 50 histologically confirmed PCa surgical specimens and matched blood. An ensemble classifier (Random Forest, Support Vector Machines, XGBoost) was trained in age-matched PCas (n = 294), and in 72 controls and 64 BPH. Classifier performance was validated in two independent sets (n = 263 PCas; n = 99 controls). We assessed the panel as a postoperative disease monitor in a radical prostatectomy cohort (RPC: n = 47). Results: A PCa-specific 27-gene panel was identified. Matched blood and tumor gene expression levels were concordant (r = 0.72, p < 0.0001). The ensemble classifier (“PROSTest”) was scaled 0%–100% and the industry-standard operating point of ≥50% used to define a PCa. Using this, the PROSTest exhibited an 85% sensitivity and 95% specificity for PCa versus controls. In two independent sets, the metrics were 92%–95% sensitivity and 100% specificity. In the RPCs (n = 47), PROSTest scores decreased from 72% ± 7% to 33% ± 16% (p < 0.0001, Mann–Whitney test). PROSTest was 26% ± 8% in 37 with normal postoperative PSA levels (<0.1 ng/mL). In 10 with elevated postoperative PSA, PROSTest was 60% ± 4%. Conclusion: A 27-gene whole blood signature for PCa is concordant with tissue mRNA levels. Measuring blood expression provides a minimally invasive genomic tool that may facilitate prostate cancer management. © 2024 The Authors. The Prostate published by Wiley Periodicals LLC.
Keywords: adult; controlled study; human tissue; aged; middle aged; human cell; major clinical study; genetics; sensitivity and specificity; adenocarcinoma; prostate specific antigen; gene expression; cohort analysis; pathology; retrospective study; tumor marker; prostate cancer; prostatic neoplasms; blood; messenger rna; rna, messenger; prostatectomy; biomarker; prostate tumor; diagnosis; psa; radical prostatectomy; real time polymerase chain reaction; predictive value; marker gene; whole blood; mrna; diagnostic test accuracy study; procedures; machine learning; support vector machine; humans; human; male; article; qpcr; random forest; melanoma cell line; liquid biopsy; biomarkers, tumor; oncogenomics; pca; solid malignant neoplasm; a-549 cell line; panc-1 cell line; lovo cell line; multigenomic liquid biopsy; rna blood level
Journal Title: Prostate
Volume: 84
Issue: 9
ISSN: 0270-4137
Publisher: John Wiley & Sons  
Date Published: 2024-06-15
Start Page: 850
End Page: 865
Language: English
DOI: 10.1002/pros.24704
PUBMED: 38571290
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Lisa   Bodei
    205 Bodei