Nestler, Tim, Wittersheim, Maike, Schaefer, Stephan, Hellmich, Martin ORCID: 0000-0001-5174-928X, Pfister, David, Odenthal, Margarete, von Brandenstein, Melanie, Buettner, Reinhard and Heidenreich, Axel (2021). Prediction of Radioresistant Prostate Cancer Based on Differentially Expressed Proteins. Urol.Int., 105 (3-4). S. 316 - 328. BASEL: KARGER. ISSN 1423-0399

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Abstract

Introduction: Although relapses after radiotherapy are common in prostate cancer (PCA) patients, those with a high risk for radioresistance cannot be identified prior to treatment yet. Therefore, this proof-of-concept study was performed to compare protein expression profiles of patients with radio-recurrent PCA to patients treated with primary radical prostatectomy separated by Gleason risk groups. We hypothesized that radio-recurrent PCA have a similar protein expression as high-risk Gleason PCA. Methods: Patient cohorts consisted of (i) 31 patients treated with salvage prostatectomy for locally recurrent PCA after primary radiotherapy and (ii) 94 patients treated with primary prostatectomy split into a Gleason high-risk (>= 4 + 3; n = 42 [44.7%]) versus a low-risk group (<= 3 + 4; n = 52 [55.3%]). Immunohistochemistry was performed using 15 antibodies with known association to radioresistance in PCA in vitro. ELISA was used for validation of selected markers in serum. Results: Androgen receptor (AR) was overexpressed in most radio-recurrent PCA (89.7%) and in most primary high-risk Gleason PCA (87.8%; p = 0.851), while only 67.3% of the low-risk group showed an expression (p = 0.017). Considering the highest Gleason pattern in primary PCA, aldo-keto reductase family 1 member C3 (AKR1C3) was most similarly expressed by patients with radio-recurrent PCA and patients with Gleason patterns 4 and 5 (p = 0.827 and p = 0.893) compared to Gleason pattern 3 (p = 0.20). These findings were supported by ELISA. Conclusion: This is the first study to evaluate protein markers in order to predict radioresistance in PCA. Our results point to AR and AKR1C3 as the most promising markers that might help stratify patients for radiotherapy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nestler, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittersheim, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaefer, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hellmich, MartinUNSPECIFIEDorcid.org/0000-0001-5174-928XUNSPECIFIED
Pfister, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Brandenstein, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heidenreich, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-569632
DOI: 10.1159/000509447
Journal or Publication Title: Urol.Int.
Volume: 105
Number: 3-4
Page Range: S. 316 - 328
Date: 2021
Publisher: KARGER
Place of Publication: BASEL
ISSN: 1423-0399
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/56963

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