Role of Engrailed-2 (EN2) as a prostate cancer detection biomarker in genetically high risk men

Abstract

Controversy surrounds the use of PSA as a biomarker for prostate cancer detection, leaving an unmet need for a novel biomarker in this setting; urinary EN2 may identify individuals with clinically relevant prostate cancer. Male BRCA1 and BRCA2 mutation carriers are at increased risk of clinically significant prostate cancer and may benefit from screening. Urine samples from 413 BRCA1 and BRCA2 mutation carriers and controls were evaluated. Subjects underwent annual PSA screening with diagnostic biopsy triggered by PSA > 3.0 ng/ml; 21 men were diagnosed with prostate cancer. Urinary EN2 levels were measured by ELISA and had a sensitivity of 66.7% and specificity of 89.3% for cancer detection. There was no statistically significant difference in EN2 levels according to genetic status or Gleason score. Urinary EN2 may be useful as a non-invasive early biomarker for prostate cancer detection in genetically high-risk individuals.

Development of a multivariable risk model integrating urinary cell DNA methylation and cell‐free RNA data for the detection of significant prostate cancer

“…It is becoming apparent from published data that urine can contain a wealth of useful cancer biomarkers within RNA, DNA, cellfree DNA, DNA methylation, and proteins. 14,22,23,39,40 However, the analyses presented here are, to the author's knowledge, the first attempt to integrate such biomarker information within the same samples for the detection of prostate cancer before biopsy. There has recently been reported that a combination of miRNA and methylation markers can be used to predict outcome following radical prostatectomy.…”

Urinary EN-2 to predict prostate cancer: Systematic review and meta-analysis

“…Of these, 15 full-text studies were excluded. Two primary studies (Morgan et al and Killick et al) 7,13 involving 597 participants met the criteria for inclusion and were analyzed (Figure 1).…”

“…The Quadas-2 items for Morgan study had low risk of bias in all domains. The second study by Killick et al 13 showed unclear risk of bias to the reference standard (prostate biopsy), since it is unclear whether all participants underwent prostate biopsy, flow and time (patient flow and time between the completion of the EN2 test and biopsy). These criteria resulted in a high risk of bias for the reference standard, with respect to applicability criteria.…”

“…Killick et al 13 Morgan et al Morgan et al 7 Killick et al Killick et al 13 Diagnostic odds ratio and meta-analysis to specifically investigate and compare EN2 as a possible biomarker for PCa. According to Pandha et al, 14 EN2 test can lead to faster diagnosis, saving thousands of lives, and has the potential to reduce the cost of disease.…”

Multiple markers for the non-invasive diagnosis and characterisation of prostate cancer

“…This performance is non-inferior, and potentially improved, when compared to PCA3 in contemporary cohorts (< 34% specificity at 90% sensitivity) and on systematic review (36% specificity and positive likelihood ratio 1.4 at 90% sensitivity) 345,346 . The robust nature of miRNAs in comparison with mRNAs makes them an attractive quarry for further investigation since their integrity is more likely to be retained in the enzymate-rich milieu that is ejaculate.…”