Gene-expression analysis of gleason grade 3 tumor glands embedded in low- and high-risk prostate cancer
- The Gleason score (GS) of prostate cancer on diagnostic biopsies is an important parameter for therapeutic decision-making. Biopsy GS under-estimates the actual GS at radical prostatectomy in a significant number of patients due to samplingartifact. The aim of this study was to identify markers that are differentially expressed in Gleason grade 3 (GG3) tumor glands embedded in GS 4 + 3 = 7 and GS 3 + 3 = 6 prostate cancer using laser capture microdissection and RNA sequencing. GG3 tumor glands embedded in nine GS 3 + 3 = 6 and nine GS 4 + 3 = 7 prostate cancers were isolated by laser capture microdissection of frozen radical prostatectomy specimens. After RNA amplification and RNA sequencing, differentially expressed genes in both GG3 components were identified by a 2log fold change > 1.0 and p-value < 0.05. We applied immunohistochemistry on a tissue micro-array representing 481 radical prostatectomy samples for further validation on protein level. A total of 501 genes were up-regulated and 421 down-regulated in GG3 glands embedded in GS 4 + 3 = 7 as compared to GS 3 + 3 = 6 prostate cancer. We selected HELLS, ZIC2 and ZIC5 genes for further validation. ZIC5 mRNA was up-regulated 17 fold (p = 8.4E–07), ZIC2 8 fold (p = 1.3E–05) and HELLS 2 fold (p = 0.006) in GG3 glands derived from GS 4 + 3 = 7. HELLS expression of ≥ 1% occurred in 10% GS < 7, 17% GS 7 and 43% GS >7 prostate cancer (p < 0.001). Using a cut-off of ≥ 1%, protein expression of ZIC5 was present in 28% GS < 7, 43% GS 7 and 57% GS > 7 cancer (p < 0.001). ZIC2 was neither associated with GS nor outcome in our validation set. HELLS was independently predictive for biochemical-recurrence after radical prostatectomy (HR 2.3; CI 1.5–3.6; p < 0.01). In conclusion, HELLS and ZIC5 might be promising candidate markers for selection of biopsy GS 6 prostate cancer being at risk for up-grading at prostatectomy.
| URN: | urn:nbn:de:kobv:526-opus4-6573 |
|---|---|
| Publisher DOI: | https://doi.org/10.18632/oncotarget.9344 |
| Author: | A. Marije Hoogland, René BöttcherORCiD, Esther VerhoefORCiD, Guido JensterORCiD, Geert J.L.H. van LeendersORCiD |
| ISSN: | 1949-2553 |
| Parent Title (English): | Oncotarget |
| Document Type: | Article |
| Language: | English |
| Year of Publication: | 2016 |
| Volume: | 7 |
| Issue: | 25 |
| First Page: | 37846 |
| Last Page: | 37856 |
| Faculties an central facilities: | Fachbereich Ingenieur- und Naturwissenschaften |
| Publishing Institution: | Technische Hochschule Wildau |
| Tag: | RNA sequencing; immunohistochemistry; laser capture microdissection; prostate cancer |
| Source: | Hoogland A. Marije, Böttcher R., Verhoef E., Jenster G., Leenders G. J.L.H. van Gene-expression analysis of gleason grade 3 tumor glands embedded in low- and high-risk prostate cancer. Oncotarget. 2016; 7: 37846-37856. Retrieved from https://www.oncotarget.com/article/9344/text/ |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 616 Krankheiten |
| Licence (German): | Creative Commons - CC BY 3.0 - Namensnennung 3.0 Unported |
| Release Date: | 2016/07/15 |



