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Prostate-Specific Membrane Antigen (PSMA) Expression Predicts Need for Early Treatment in Prostate Cancer Patients
Elham Ahmadi1,2,3, Simon Wang1,3, Mohammad Gouran-Savadkoohi1
1Department of Oncology, McMaster University, Hamilton, ON L8S 4L8, Canada.
International Journal of Molecular Sciences
|November 25, 2023
Summary
Metabolic enzyme expression, including Prostate-Specific Membrane Antigen (PSMA), in prostate cancer biopsies may predict progression. Elevated PSMA in malignant glands independently predicts faster progression on active surveillance.
Area of Science:
- Oncology
- Metabolic pathways
- Biomarker discovery
Background:
- Metabolic dysregulation is an early hallmark of cancer development.
- Identifying early biomarkers for prostate cancer (PC) progression is crucial for active surveillance management.
- Enzymes in de novo lipogenesis, glucose uptake, and folate metabolism are implicated in carcinogenesis.
Purpose of the Study:
- To evaluate the expression of ATP-citrate lyase (ACLY), Glucose Transporter 1 (GLUT1), and Prostate-Specific Membrane Antigen (PSMA) as potential biomarkers for early PC progression.
- To correlate the expression levels of these metabolic enzymes in baseline diagnostic biopsies with time remaining on active surveillance.
- To determine if these markers can predict rapid progression in patients with low-risk PC.
Main Methods:
- Expression of PSMA, GLUT1, and ACLY was assessed using immunohistochemistry (IHC) on baseline prostate biopsy tissues.
- Quantification of enzyme expression was performed using a Histologic Score in both benign and malignant glands.
- Statistical analysis, including univariate and multivariate analyses, was used to compare expression levels with time-on-active surveillance (time-on-AS).
Main Results:
- All three markers (PSMA, GLUT1, ACLY) showed a trend towards elevated expression in malignant compared to benign glands, with ACLY showing statistical significance.
- Increased malignant PSMA and GLUT1 expression were associated with significantly shorter time-on-AS on univariate analysis.
- Multivariate analysis identified overexpression of PSMA in malignant glands as an independent predictor of early PC progression (p = 0.006).
Conclusions:
- Expression levels of metabolic enzymes, particularly PSMA, in baseline prostate biopsies may serve as valuable biomarkers for predicting early PC progression.
- Prostate-Specific Membrane Antigen (PSMA) shows promise as an independent predictor of risk for progression in patients managed on active surveillance.
- Further systematic studies are warranted to validate PSMA as a predictive biomarker for prostate cancer progression.
