Explication of the roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) as diagnostic and predictor tools for prostate cancer in equivocal PSA range of 4–10 ng/mL

Abstract

Background Prostate cancer (PCa) is one of the most commonly encountered cancers and the leading cause of death worldwide. Currently used biomarkers accounts difficulties in discriminating benign from malignant cases or predicting outcome, so investigating new biomarkers performance is needed. Objectives Assessment of diagnostic and predictor roles of prostate health index (PHI) and urokinase plasminogen activator (uPA) in PCa. Methods 194 males with initial tPSA of 4–10 ng/mL were categorized into three groups: PCa, benign prostatic hyperplasia (BPH) and healthy control. Serum levels of tPSA, fPSA, p2PSA, and uPA were performed by ELISA with calculation of PHI as (p2PSA/fPSA) × √PSA. Results PHI and uPA were significantly higher in PCa patients relevant to BPH and healthy control (p ≤ 0.001). Both markers outperformed all assessed biomarkers and showed the highest area under the curve (AUC) in ROC curve analysis. Both were significantly higher in PCa patients with {Gleason score ≥ 7, late stages (cT2b,c; T3), LN extension and distant metastasis}relative to their counterparts. Additionally, PHI and uPA and were independent predictors of distant metastasis and Gleason score ≥ 7, while PHI was predictor of LN invasion (β = 0.25, p = 0.004). Conclusion PHI and uPA would be of potential value in discriminating between PCa, BPH and healthy men in addition, both are promising as independent predictors of adverse pathological features.

Current understanding of prostate cancer biomarkers

“…Kamel продемонстрирована высокая прогностическая способность PHI и урокиназного активатора плазминогена для дифференциальной диагностики РПЖ, доброкачественной гиперплазии ПЖ и нормы при уровне общего ПСА 4-10 нг/мл (p ≤0,001). PHI и урокиназный активатор плазминогена оказались независимыми предикторами отдаленных метастазов при РПЖ с суммой баллов по шкале Глисона ≥7, а PHI -предиктором инвазии опухоли в лимфатические узлы (p = 0,004) [16].…”

PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer

“…As the tumor becomes more aggressive and the disease is more advanced, the level of PHI increases, and if there are positive margins, it remains high even after radical prostatectomy. PHI proved to be an independent predictor for diagnosis and prognosis [ 43 ].…”