This work aimed to analyse the expression of and correlation between folate transporters FOLR1, FOLR2, SLC19A1 (reduced folate carrier, RFC), and FOLH1 (PSMA mRNA) in a large cohort of prostate cancer samples, with the goal of better understanding the nature of aggressive disease with low PSMA expression.
A total of 55 329 radical prostatectomy (RP) tumour specimens tested with the Decipher prostate genomic classifier (Veracyte, CA) were identified from the Decipher GRID database (NCT02609269). Transcriptome-wide mRNA expression and baseline clinicopathologic data were retrieved. Logistic regression assessed associations between gene expression, pathological Gleason grade group (GG) 4-5, lymph node invasion (LNI), seminal vesicle invasion (SVI), and very high Decipher score (>0.85).
This cohort had a median age of 65 years and PSA of 4.9 ng/mL. FOLR1and FOLR2 showed no correlation with PSMA. High FOLR2 and RFC were associated with very high Decipher scores and GG4-5. In the lowest 10% PSMA group, high FOLR2 correlated with high Decipher scores, GG4-5, LNI, and SVI (all p < 0.001). Limitations include the retrospective design and the inability to distinguish FR-β expression from immune cell infiltration.
Our large-scale study of transcriptome demonstrates FOLR2 gene expression is associated with aggressive prostate cancer in samples with low expression of PSMA. Future prediction of disease risk could be enhanced by using FOLR2 as a molecular target for identifying aggressive prostate cancer in cases of low PSMA.
BJUI compass. 2026 May 21*** epublish ***
Ashorne K Mahenthiran, Burak Akgul, Mohammed Alshalalfa, Mark A Green, Giovanna A Giannico, Elai Davicioni, Daniel A Sidhom, Michael O Koch, Clinton D Bahler
Department of Urology Indiana University School of Medicine Indianapolis Indiana USA., Department of Research and Development Veracyte Inc. South San Francisco California USA., Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis Indiana USA., Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis Indiana USA.