Birker, I.L. (2012) The diagnostic performance of prostate cancer related biomarkers in urinary exosomes and the necessity of a digital rectal examination. thesis, Medicine.
Full text available on request.Abstract
Background: Prostate cancer (PCa) is the most frequent solid malignancy among males in economically developed countries and the third leading cause of cancer death in males. Prostate Specific Antigen (PSA) testing has increased PCa detection. However, one of the main drawbacks has been its low specificity causing over diagnosis and overtreatment. This emphasizes the need for additional markers, preferably non-invasive, to identify men at high risk of clinically significant PCa. Therefore this study investigates known and new biomarkers in two urinary fractions. Methods: Urine samples were collected before and after digital rectal examination (DRE) from men who were selected for prostate biopsies based on elevated serum PSA levels (≥ 3 ng/mL) and/or abnormal DRE. Two urinary fractions, exosomes and celpellets, were isolated by ultra centrifugation and filtration. After RNA extraction and whole transcript amplification the expression level of several biomarkers were measured by real-time PCR (q-PCR): PCA3, TMPRSS2-ERG, PSA, HPRT and three recently discovered biomarkers: NGPCBM19, NGPCBM8, and NGPCBM14. The quantity of these biomarkers was compared between samples taken before and after DRE, and their diagnostic performance was analysed in both urinary fractions. Results: 31 patients (14 positive, 16 negative, 1 without biopsies) were included. Five celpellets were excluded because of deposits and 13 (10 pre-, 3 post DRE) because the samples were non-evaluable. Significant differences (p<0.05) in biomarker expression were found between samples taken before and after DRE for PSA, HPRT, PCA3 and NGPCBM14 in celpellets and additionally for NGPCBM8 in the exosomes. ROC-curves showed a good diagnostic performance of the biomarkers in the celpellets after DRE (AUC 0.616 - 0.835). In the exosomes, PSA and HPRT showed an inverse correlation (AUC 0.279 and 0.135) with positive biopsy outcomes, the other biomarkers showed no diagnostic correlation (AUC 0.464 - 0.577). Conclusion: All biomarkers can be measured in the exosomes and performing a DRE is essential. The diagnostic performance of these biomarkers in the exosomes is different from the celpellet, thus their diagnostic contribution remains unknown. But because exosomes have different advantages over celpellets, it makes them an interesting candidate for future biomarker research.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Nijholt, Dr. I.M. and Isala Klinieken, Zwolle |
| Supervisor name: | Reijke, Dr. Th.M. de and Department of Urology - AMC, Amsterdam |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:58 |
| Last Modified: | 25 Jun 2020 10:58 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1836 |
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