Mitophagy-associated genes PINK1 and PARK2 are independent prognostic markers of survival in papillary renal cell carcinoma and associated with aggressive tumor behavior.

Autor: Simon AG; Institute of Pathology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Tolkach Y; Institute of Pathology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Esser LK; Institute of Pathology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Ellinger J; Department of Urology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Stöhr C; Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Germany., Ritter M; Department of Urology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Wach S; Department of Urology, University Hospital Erlangen, Krankenhausstr. 12, 91054, Erlangen, Germany., Taubert H; Department of Urology, University Hospital Erlangen, Krankenhausstr. 12, 91054, Erlangen, Germany., Stephan C; Department of Urology, University Hospital Berlin-Charité, Charitéplatz 1, 10117, Berlin, Germany., Hartmann A; Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8-10, 91054, Erlangen, Germany., Kristiansen G; Institute of Pathology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Branchi V; Department of General, Abdominal, Thoracic and Vascular Surgery, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany., Toma MI; Institute of Pathology, University Hospital Bonn, Venusberg-Campus 1, 53127, Bonn, Germany. marieta.toma@ukbonn.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Nov 02; Vol. 10 (1), pp. 18857. Date of Electronic Publication: 2020 Nov 02.
DOI: 10.1038/s41598-020-75258-4
Abstrakt: The aim of this study was to investigate the mitophagy-related genes PINK1 and PARK2 in papillary renal cell carcinoma and their association with prognosis. In silico data of PINK1 and PARK2 were analyzed in TCGA cohorts of papillary renal cell carcinoma comprising 290 tumors and 33 corresponding non-neoplastic renal tissues. Protein expression data from a cohort of 95 papillary renal cell carcinoma patients were analyzed and associated with clinical-pathological parameters including survival. PINK1 and PARK2 were significantly downregulated in papillary renal cell carcinoma at transcript and protein levels. Reduced transcript levels of PINK1 and PARK2 were negatively associated with overall survival (p < 0.05). At the protein level, PARK2 and PINK1 expression were positively correlated (correlation coefficient 0.286, p = 0.04) and reduced PINK1 protein expression was prognostic for shorter survival. Lower PINK1 protein levels were found in tumors with metastases at presentation and in tumors of higher pT-stages. The multivariate analysis revealed mRNA expression of PINK1 and PARK2 as well as PINK1 protein expression as independent prognostic factors for shorter overall survival. The downregulation of PINK1 is a strong predictor of poor survival in papillary renal cell carcinoma. Immunohistochemical PINK1 expression in resected pRCC should be considered as an additional prognostic marker for routine practice.
Databáze: MEDLINE
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