A Novel Combination of Serum Markers in a Multivariate Model to Help Triage Patients Into “Low-” and “High-Risk” Categories for Prostate Cancer

Christopher McNally, Joanne Watt, Mary Jo Kurth, John V. Lamont, Tara C. B. Moore, Peter Fitzgerald, Hardev Pandha, Declan J McKenna, Mark Ruddock

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Background: Almost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies. Materials and Methods: Serum samples and clinical information were collected from N = 125 age-matched patients (n = 61 non-PCa and n = 64 PCa) and analyzed using Biochip Array Technology on high-sensitivity cytokine array I (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, INFγ, EGF, and VEGF), cerebral array II (CRP, D-dimer, neuron-specific enolase, and sTNFR1), and tumor PSA oncology array (fPSA, tPSA, and CEA). Results: The data showed that 11/19 (68.8%) markers were significantly different between the non-PCa and the PCa patients. A combination of EGF, log 10 IL-8, log 10 MCP-1, and log 10 tPSA significantly improved the predictive potential of tPSA alone to identify patients with PCa (DeLong, p < 0.001). This marker combination had an increased area under the receiver operator characteristic (0.860 vs. 0.700), sensitivity (78.7 vs. 68.9%), specificity (76.5 vs. 67.2%), PPV (76.2 vs. 66.7%), and NPV (79.0 vs. 69.4%) compared with tPSA. Conclusions: The novel combination of serum markers identified in this study could be employed to help triage patients into “low-” and “high-risk” categories, allowing general practitioners to improve the management of patients in primary care settings and potentially reducing the number of referrals for unnecessary, invasive, and costly treatments.

Original languageEnglish
Article number837127
Pages (from-to)1-8
Number of pages8
JournalFrontiers in Oncology
Publication statusPublished (in print/issue) - 19 May 2022

Bibliographical note

Funding Information:
The authors declare that this study received funding from Randox Laboratories Ltd as part of the Randox Laboratories Ltd – Ulster University PhD Academy Studentship. Randox had the following involvement in the study: analysis of patient samples, statistical analysis, supervision of the project, preparation of the manuscript, and the decision to publish.

Publisher Copyright:
Copyright © 2022 McNally, Watt, Kurth, Lamont, Moore, Fitzgerald, Pandha, McKenna and Ruddock.


  • Oncology
  • algorithm
  • EGF
  • fPSA
  • IL-8
  • marker
  • MCP-1
  • prostate cancer
  • tPSA


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