PYGOPUS2 expression in prostatic adenocarcinoma is a potential risk stratification marker for PSA progression following radical prostatectomy
| Autor: | John Thoms, Satoko Aoki, Shahgul Anwar, Luis Gai, Paul Popadiuk, Catherine Popadiuk, Andrea Simmonds, Kenneth R. Kao, Paola Gonzales-Aguirre, Zhijian He, Satya Challa, Kim Voisey, Emily Fitzgerald, Phillip G. P. Andrews |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Oncology Pathology Time Factors medicine.medical_treatment Kaplan-Meier Estimate urologic and male genital diseases Prostate cancer 0302 clinical medicine Risk Factors Prostate Tissue microarray Prostatectomy Intracellular Signaling Peptides and Proteins General Medicine Immunohistochemistry Up-Regulation 3. Good health Prostate-specific antigen Treatment Outcome medicine.anatomical_structure 030220 oncology & carcinogenesis Disease Progression Adenocarcinoma Kallikreins RNA Interference Biochemical recurrence medicine.medical_specialty Biology Transfection Disease-Free Survival Pathology and Forensic Medicine 03 medical and health sciences Predictive Value of Tests Cell Line Tumor Internal medicine Biomarkers Tumor medicine Humans Cell Proliferation Neoplasm Staging Proportional Hazards Models Prostatic Neoplasms Cancer Prostate-Specific Antigen medicine.disease 030104 developmental biology Tissue Array Analysis Multivariate Analysis Neoplasm Grading |
| Zdroj: | Journal of Clinical Pathology. 71:402-411 |
| ISSN: | 1472-4146 0021-9746 |
| DOI: | 10.1136/jclinpath-2017-204718 |
| Popis: | AimsProstate cancer (PrCa) is the most frequently diagnosed non-cutaneous cancer in men. Without clear pathological indicators of disease trajectory at diagnosis, management of PrCa is challenging, given its wide-ranging manifestation from indolent to highly aggressive disease. This study examines the role in PrCa of the Pygopus (PYGO)2 chromatin effector protein as a risk stratification marker in PrCa.MethodsRNA expression was performed in PrCa cell lines using Northern and RT-PCR analyses. Protein levels were assessed using immunoblot and immunofluorescence. Immunohistochemistry was performed on tissue microarrays constructed from radical prostatectomies with 5-year patient follow-up data including Gleason score tumour staging, margin and lymph node involvement and prostate serum antigen (PSA) levels. Biochemical recurrence (BR) was defined as a postoperative PSA level of >0.2 nL. Univariate and multivariate analyses were performed using SAS and Kaplan-Meier curves using graphPad (Prism).ResultsIn vitro depletion of PYGO2 by RNAi in both androgen receptor positive and negative PrCa cell lines attenuated growth and reduced Ki67 and 47S rRNA expression, while PYGO2 protein was localised to the nuclei of tumours as determined by immunohistochemistry. High expression levels of PYGO2 in tumours (n=156) were correlated with BR identified as PSA progression, after 7-year follow-up independent of other traditional risk factors. Most importantly, high PYGO2 levels in intermediate grade tumours suggested increased risk of recurrence over those with negative or weak expression.ConclusionOur data suggest that elevated PYGO2 expression in primary prostate adenocarcinoma is a potential risk factor for BR. |
| Databáze: | OpenAIRE |
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