Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics

Logan, Jessica M.; Malone, Victoria; O’Leary, John J.; Brooks, Doug A.

doi:10.3390/ijms262411786

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Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics

¹

Clinical and Health Sciences, University of South Australia, Adelaide 5000, Australia

²

Department of Pathology, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland

³

Department of Histopathology, Trinity College Dublin, D02 PN40 Dublin, Ireland

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(24), 11786; https://doi.org/10.3390/ijms262411786

Submission received: 16 October 2025 / Revised: 28 November 2025 / Accepted: 2 December 2025 / Published: 5 December 2025

(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Pathology, Diagnostics, and Therapeutics)

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Abstract

Despite prostate cancer being one of the most common malignancies in men, its pathological diagnosis remains plagued by inter-observer variability and diagnostic ambiguity. Traditional morphological assessment and currently available biomarkers such as PSA (Prostate-Specific Antigen), AMACR (Alpha methylacyl CoA racemase), and p63 suffer from poor specificity and clinical reliability. In this review, we present a pathogenesis-guided biomarker discovery strategy that led to the development of a clinically validated biomarker panel—Appl-1, Sortilin, and Syndecan-1. These biomarkers, which reflect fundamental biological processes within the endosome–lysosome system, offer improved diagnostic precision and prognostic utility for patients with prostate cancer. This review discusses the rationale behind their discovery, the multidisciplinary approach that enabled it, the evidence supporting their use, and their implementation in U.S. clinical practice as a lab-developed test (LDT). We propose this approach as a new diagnostic standard that bridges mechanistic insight with real-world application.

Keywords: prostate cancer; biomarkers; diagnosis; pathogenesis

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MDPI and ACS Style

Logan, J.M.; Malone, V.; O’Leary, J.J.; Brooks, D.A. Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics. Int. J. Mol. Sci. 2025, 26, 11786. https://doi.org/10.3390/ijms262411786

AMA Style

Logan JM, Malone V, O’Leary JJ, Brooks DA. Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics. International Journal of Molecular Sciences. 2025; 26(24):11786. https://doi.org/10.3390/ijms262411786

Chicago/Turabian Style

Logan, Jessica M., Victoria Malone, John J. O’Leary, and Doug A. Brooks. 2025. "Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics" International Journal of Molecular Sciences 26, no. 24: 11786. https://doi.org/10.3390/ijms262411786

APA Style

Logan, J. M., Malone, V., O’Leary, J. J., & Brooks, D. A. (2025). Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics. International Journal of Molecular Sciences, 26(24), 11786. https://doi.org/10.3390/ijms262411786

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Pathogenesis-Guided Biomarker Assessment: A Shift in Prostate Cancer Diagnostics

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