Systematic expression analysis of the mitochondrial respiratory chain protein subunits identifies COX5B as a prognostic marker in clear cell renal cell carcinoma.

OBJECTIVE:To analyze the expression of mitochondrial respiratory chain protein subunits in clear cell renal cell carcinoma. METHODS:Possible prognostic candidates were determined using The Cancer Genome Atlas database (n = 605). The database provided valid messenger ribonucleic acid expression data for 93 genes encoding for the subunits. Selected subunits were further investigated at the messenger ribonucleic acid and protein level by real-time polymerase chain reaction, western blot and immunohistochemistry with the cohorts of the University Hospital Bonn. RESULTS:The Cancer Genome Atlas messenger ribonucleic acid expression data indicated univariate and multivariate prognostic impact for seven subunits (NDUFS8, NDUFS7, COX5B, COX6B1, SDHD, COX15 and COX19). Using real-time polymerase chain reaction, significant downregulation (P < 0.05, n = 74) could be shown for COX5B, COX6B1, NDUFS7 and NDUF8 in clear cell renal cell carcinoma tissue. Survival analysis of polymerase chain reaction data showed a non-significant relationship (P = 0.067) of high COX5B expression and poor overall survival. Western blot (n = 8) and immunohistochemistry analysis (n = 167) confirmed significant COX5B downregulation on the protein level. Immunohistochemistry analysis identified COX5B as a prognostic marker for overall (P = 0.017) and cancer-specific survival (P = 0.042). CONCLUSIONS:The present study findings suggest downregulation of additional subunits of mitochondrial respiratory chain proteins in clear cell renal cell carcinoma. Remarkably, COX5B, a subunit of the respiratory chain complex IV, can be identified as a novel prognostic marker.

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