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

Institute of Cancer Research, Sutton, Surrey, UK.
Scientific Reports (Impact Factor: 5.58). 06/2013; 3:2059. DOI: 10.1038/srep02059
Source: PubMed


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.

Download full-text


Available from: Dafydd Gareth Evans, Jan 25, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Extensive efforts to identify a clinically useful biomarker for the diagnosis of prostate cancer have resulted in important insights into the biology of the disease, but no new test has been approved by regulatory authorities. The unmet need has also shifted to identifying biomarkers that not only diagnose prostate cancer but also indicate whether the patient has 'significant' disease. EN2 is a homeobox-containing transcription factor secreted specifically by prostate cancers into urine, where it can be detected by a simple ELISA assay. A number of studies have demonstrated the enormous potential of EN2 to address this unmet need and provide the urologist with a simple, cheap and efficient prostate cancer biomarker.
    Full-text · Article · Dec 2013 · Biomarkers in Medicine
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND AND METHODS Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and amplification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS classifications and in relation to whole gland histopathology following radical prostatectomy. Multivariate logistic regression modeling and clinical risk (incorporating standard clinicopathological variables) were performed for all ejaculate-based markers.RESULTSWhile Hepsin alone was not of predictive value, the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate composite score based on multivariate logistic regression, was shown to be a better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676) and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659) risk stratification criteria as classified using prostate biopsies. It was also possible to analyse a subgroup of patients for miRNA expression with miR-200c (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while a combination of serum PSA, miR-200c, and miR-125b further improved prediction for prostate cancer status when compared to PSA alone determined by biopsy (AUC 0.869 vs. 0.672; P < 0.05), and risk (D'Amico/PRIAS) as well as by radical prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by biopsy, at a sensitivity of 90%, the specificity of the test increased from 11% for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b.CONCLUSIONS These results show that use of a combination of different types of genetic markers in ejaculate together with serum PSA are at least as sensitive as those reported in DRE urine. Furthermore, a combination of serum PSA and selected miRNAs improved prediction of prostate cancer status. This approach may be helpful in triaging patients for MRI and biopsy, when confirmed by larger studies. Prostate © 2015 Wiley Periodicals, Inc.
    Full-text · Article · Jan 2015 · The Prostate
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The discovery of protein biomarkers that reflect the biological state of the body is of vital importance to disease management. Urine is an ideal source of biomarkers that provides a non-invasive approach to diagnosis, prognosis and prediction of diseases. Consequently, the study of the human urinary proteome has increased dramatically over the last 10 years, with many studies being published. This review focuses on urinary protein biomarkers that have shown potential, in initial studies, for diseases affecting the urogenital tract, specifically chronic kidney disease and prostate cancer, as well as other non-urogenital pathologies such as breast cancer, diabetes, atherosclerosis and osteoarthritis. PubMed was searched for peer-reviewed literature on the subject, published in the last 10 years. The keywords used were "urine, biomarker, protein, and/or prostate cancer/breast cancer/chronic kidney disease/diabetes/atherosclerosis/osteoarthritis". Original studies on the subject, as well as a small number of reviews, were analysed including the strengths and weaknesses, and we summarized the performance of biomarkers that demonstrated potential. One of the biggest challenges found is that biomarkers are often shared by several pathologies so are not specific to one disease. Therefore, the trend is shifting towards implementing a panel of biomarkers, which may increase specificity. Although there have been many advances in urinary proteomics, these have not resulted in similar advancements in clinical practice due to high costs and the lack of large data sets. In order to translate these potential biomarkers to clinical practice, vigorous validation is needed, with input from industry or large collaborative studies.
    Preview · Article · Feb 2015 · Biochemia Medica
Show more