Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun;84(9):850-865.
doi: 10.1002/pros.24704. Epub 2024 Apr 3.

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

Irvin M Modlin  1 , Mark Kidd  2 , Ignat A Drozdov  3 , Martin Boegemann  4 , Lisa Bodei  5 , Jolanta Kunikowska  6 , Anna Malczewska  7 , Christof Bernemann  4 , Srinivas V Koduru  2 , Kambiz Rahbar  8
Affiliations

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

Irvin M Modlin et al. Prostate. 2024 Jun.

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.

Keywords: PCa; PSA; adenocarcinoma; biomarker; diagnosis; liquid biopsy; mRNA; prostate cancer; qPCR; whole blood.

PubMed Disclaimer

References

REFERENCES

    1. Sandhu S, Moore CM, Chiong E, Beltran H, Bristow RG, Williams SG. Prostate Cancer. Lancet; 2021.
    1. Gillessen S, Attard G, Beer TM, et al. Management of patients with advanced prostate cancer: report of the advanced prostate cancer consensus conference 2019. Eur Urol. 2020;77(4):508‐547.
    1. Casanova‐Salas I, Athie A, Boutros PC, et al. Quantitative and qualitative analysis of blood‐based liquid biopsies to inform clinical decision‐making in prostate cancer. Eur Urol. 2021;79(6):762‐771.
    1. Oesterling JE. Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate. J Urol. 1991;145(5):907‐923.
    1. Leal J, Welton NJ, Martin RM, et al. Estimating the sensitivity of a prostate cancer screening programme for different PSA cut‐off levels: a UK case study. Cancer Epidemiol. 2018;52:99‐105.

Publication types