Urine Extracellular Vesicle GATA2 mRNA Discriminates Biopsy Result in Men with Suspicion of Prostate Cancer

Extracellular vesicles as a source of prostate cancer biomarkers in liquid biopsies: a decade of research

“… Biomarker Biofluid EV isolation Target detection Number of patients Comparison Performance Ref. mRNAs PCA3 ERG SPDEF Urine Urine clinical sample concentration kit (Exosome diagnostics) RT-qPCR 195 men at initial biopsy GS ≤ 6 vs. GS ≥ 7 RNAs + SOC AUC 0.8 [ 157 ] Men undergoing biopsy: Training set: 255 Testing set: 519 Training set: mRNAs + SOC AUC 0.77 Testing set: RNAs + SOC AUC 0.73 [ 155 ] 519 men at initial biopsy RNAs + SOC AUC 0.71 [ 159 ] PCA3 ERG SPDEF GATA2 Urine Ultracentrifugation RT-qPCR Men undergoing initial biopsy: Training set: 52 Testing set: 165 PCa vs. healthy RNAs + SOC AUC: Training set: 0.88 Testing set: 0.72 [ 161 ] GS ≤ 6 vs. GS ≥ 7 RNAs + SOC AUC: Training set: 0.9 Testing set: 0.75 PCA3 PRAC Urine Ultracentrifugation RT-qPCR 89 men undergoing biopsy PCa vs. healthy AUC 0.723 [ 127 ] GS ≤ 6 vs. GS ≥ 7 AUC 0.736 PCA3 PCGEM1 Urine Exosome RNA isolation kit (Norgen) RT-qPCR 271 men undergoing RP GS ≤ 6 vs. GS ≥ 7 RNAs + SOC AUC 0.875 [ 162 ] BIRC5 ERG PCA3 TMPRSS2:ERG TMPRSS2 Urine 100 K MWCO filtration concentrator (Millipore) RT-qPCR 47 PCa 19 healthy men PCa vs. healt...…”

“…Later studies have used non-DRE urine and ultrafiltration centrifugation to concentrate the vesicles and detect PCA3 and ERG [ 158 , 159 ]. Additionally, a recent independent study including 217 men proposed that the addition of GATA2 to this model could improve the detection of high-risk PCa [ 161 ]. Further studies with urinary EVs have reported that the ratio between PCA3 and PCa-susceptibility candidate (PRAC) can differentiate both between healthy men and PCa patients and between GS ≤ 6 and GS ≥ 7 in a cohort of 89 individuals [ 127 ] and that PCA3, together with PCGEM1, can be used to distinguish between favourable and unfavourable intermediate tumours (GS 3 + 4 vs GS 4 + 3 or higher) in a racially diverse cohort of 271 patients [ 162 ].…”

Nanomaterials-Based Urinary Extracellular Vesicles Isolation and Detection for Non-invasive Auxiliary Diagnosis of Prostate Cancer

“…Similarly, for patients with PCa after prostatectomy, the GATA2 and TMPRSS2: ERG expression levels of urinary EVs also showed a significant downward trend or even disappeared, which were related to the expression levels of GATA2 and TMPRSS2: ERG in prostate tissue. In addition, when these two mRNAs were used in combination with PCA3, the ability to recognize aggressive PCa can be improved and 91.2% of unnecessary biopsies can be avoided, which helps to reduce the over-diagnosis of patients with PCa (35,117). Moreover, several combination panels, such as the PCA3 and PCGEM1 gene panels and the combination of ERG, PCA3, SPDEF genes, and standard of care (SOC), were also capable of identifying high-grade PCa, and all of them have better diagnostic performance than using SOC alone (34,115,118).…”

Molecular Biomarkers for the Detection of Clinically Significant Prostate Cancer: A Systematic Review and Meta-analysis

“…Three of these could not be retrieved [17] , [18] , [19] . Sixty-five studies [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , reported in 69 articles [20] , [21] ,…”

“…Previous prostate biopsy (previous 6 mo) 5. Previous PCA3 Caucasians (79) African Americans (14) Other ethnicities (7) 7.00 ± 15.00 c 297 67 26 64 8 Caucasians (82) African Americans (11) Other ethnicities (7) 10.00 ± 10.00 c Woo (2020) [81] 52 20 13 Gleason ≥7 67.80 NR 51–83 1. Scheduled to biopsy by elevated PSA or suspicious DRE NR Caucasians 8.60 (1.50–39.20) b 165 107 83 66.50 47–82 Caucasians (92.5) 7.90 (0.10–46.80) b Wu (2019) [89] 635 272 207 Gleason ≥7 69 NR 61–76 NR 1.…”