Urine Exosomal AMACR Is a Novel Biomarker for Prostate Cancer Detection at Initial Biopsy

Abstract

ObjectivesThe aim of this study is to identify and validate urine exosomal AMACR (UE-A) as a novel biomarker to improve the detection of prostate cancer (PCa) and clinically significant PCa (Gleason score ≥ 7) at initial prostate biopsy.MethodsA total of 289 first-catch urine samples after the digital rectal exam (DRE) were collected from patients who underwent prostatic biopsy, and 17 patients were excluded due to incomplete clinical information. Urine exosomes were purified, and urinary exosomal AMACR (UE-A) was measured by enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of UE-A was evaluated by receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and waterfall plots.ResultsThe expression of AMACR in PCa and csPCa was significantly higher than that in BPH and non-aggressive (p < 0.001). The UE-A presented good performance in distinguishing PCa from BPH or BPH plus non-significant PCa (nsPCa) from csPCa with an area under the ROC curve (AUC) of 0.832 and 0.78, respectively. The performance of UE-A was further validated in a multi-center cohort of patients with an AUC of 0.800 for detecting PCa and 0.749 for detecting csPCa. The clinical utility assessed by DCA showed that the benefit of patients using UE-A was superior to PSA, f/t PSA, and PSAD in both the training cohort and the validation cohort in terms of all threshold probabilities. Setting 95% sensitivity as the cutoff value, UE-A could avoid 27.57% of unnecessary biopsies, with only 4 (1.47%) csPCa patients missed.ConclusionsWe demonstrated the great performance of UE-A for the early diagnosis of PCa and csPCa. UE-A could be a novel non-invasive diagnostic biomarker to improve the detection of PCa and csPCa.

Deep learning assisted identification of ATP5J and ALDH1A2 combination in RNA-sequencing data as a novel specific potential diagnostic biomarker in prostate cancer

“…AMACR is a well-known diagnostic biomarker in PCa and different studies confirmed its upregulation in prostate cancer. AMACR is a reliable biomarker and could accurately distinguish prostate cancer from a normal sample which is a validation for our results (13,20). ALDH1A2 is significantly downregulated in prostate cancer which was validated in other PCa datasets including Cambridge, CancerMap, CIT, Taylor, and many other GEO datasets such as GSE29079, GSE6956, GSE32269, GSE59745, and GSE79021 (23).…”

“…We assessed prior reports of these genes as diagnostic biomarkers in PCa. AMACR is a well-known biomarker of PCa which could be found in urine exosomes (13,20). Our data showed more validation of the potency of AMACR as a novel diagnostic biomarker.…”

Proteomic-based stratification of intermediate-risk prostate cancer patients

“…AMACR has a major role in fatty acid oxidation and has previously been found to be overexpressed in PCa at the proteomic and transcriptomic levels, confirming its validity as a potential biomarker 56,57,58,59 . Among the four FDA-approved targetable proteins, MDH2 is known to be overexpressed in PCa and castrate-resistant PCa (CRPC), highlighting its role in PCa progression 23 and resistance to chemotherapy 60 .…”

Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives

“…AMACR has also been evaluated as a novel diagnostic marker to detect PCa during screening tests. In a recent study by Xin et al [ 157 ], the authors, after conducting digital rectal examinations, collected first-catch urine samples from patients who also underwent prostate biopsy. The urinary exosomal AMACR (UE-A) was then measured using ELISA.…”