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Abstract
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.
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Details
1 University Hospital Bonn, Institute of Pathology, Bonn, Germany (GRID:grid.15090.3d) (ISNI:0000 0000 8786 803X)
2 University Hospital Bonn, Department of Urology, Bonn, Germany (GRID:grid.15090.3d) (ISNI:0000 0000 8786 803X)
3 University Hospital Erlangen, Institute of Pathology, Erlangen, Germany (GRID:grid.411668.c) (ISNI:0000 0000 9935 6525)
4 University Hospital Erlangen, Department of Urology, Erlangen, Germany (GRID:grid.411668.c) (ISNI:0000 0000 9935 6525)
5 University Hospital Berlin-Charité, Department of Urology, Berlin, Germany (GRID:grid.6363.0) (ISNI:0000 0001 2218 4662)
6 University Hospital Bonn, Department of General, Abdominal, Thoracic and Vascular Surgery, Bonn, Germany (GRID:grid.15090.3d) (ISNI:0000 0000 8786 803X)