Serum 20S proteasome is elevated in patients with renal cell carcinoma and associated with poor prognosis

• Published in: British journal of cancer Vol. 106; no. 5; pp. 904 - 908
• Main Authors: de Martino, M, Hoetzenecker, K, Ankersmit, H J, Roth, G A, Haitel, A, Waldert, M, Klatte, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.02.2012; Nature Publishing Group
• Subjects: 631/45/474/2085; 692/699/67/589/1588/1351; 692/700/139; 692/700/1750; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - diagnosis; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Carcinoma, Renal Cell - secondary; Cell cycle; Drug Resistance; Enzymes; Epidemiology; Female; Growth factors; Humans; Hypoxia; Indoles - pharmacology; Indoles - therapeutic use; Kidney cancer; Kidney Neoplasms - blood; Kidney Neoplasms - diagnosis; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Kidneys; Male; Medical prognosis; Medical research; Medical sciences; Metastasis; Molecular Diagnostics; Molecular Medicine; Neoplasm Metastasis - pathology; Nephrology. Urinary tract diseases; Oncology; Prognosis; Proteasome Endopeptidase Complex - biosynthesis; Proteasome Endopeptidase Complex - blood; Proteins; Pyrroles - pharmacology; Pyrroles - therapeutic use; Review boards; Signal transduction; Survival Analysis; Thoracic surgery; Tumors; Tumors of the urinary system; Urology; Austria; hypoxia; renal cancer; diagnosis; 20S proteasome; prognosis; Kidney disease; Human; Multicatalytic endopeptidase complex; Oxygen; Urinary system disease; Carcinoma; Prognosis; Enzyme; Malignant tumor; Peptidases; Cancerology; Kidney cancer; Hydrolases; Grawitz tumor; Hypoxia; Serum; Diagnosis; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.20

Background: To date, no reliable serum marker for clear cell renal cell carcinoma (CCRCC) is available. The aim of this study was to evaluate the putative significance of circulating 20S proteasome levels. Methods: Preoperative 20S proteasome serum levels were determined in 113 CCRCC patients and 15 healthy controls by a sandwich enzyme-linked immunosorbent assay. Associations with CCRCC, pathological variables, disease-specific survival (DSS), and response to sunitinib were evaluated. Results: Median 20S proteasome levels were higher in CCRCC patients than in healthy controls (4.66 vs 1.52  μ g ml −1 , P <0.0001). The area under the receiver operating characteristics curve curve was 87.1%. The 20S proteasome levels were associated with symptoms ( P =0.0008), distant metastases ( P =0.0011), grade ( P =0.0247), and necrosis ( P =0.0462). The 20S proteasome levels were identified as a prognostic factor for DSS in both univariable (hazards ratio 1.21, P <0.001) and multivariable (hazards ratio 1.17, P =0.0015) survival analysis. In patients responding to sunitinib, 20S proteasome levels were lower than in patients with stable disease and progressive disease. Conclusion: This study demonstrates for the first time that increased 20S proteasome levels are associated with CCRCC, advanced disease, and poor prognosis. Routine use of this marker may allow better diagnosis, risk stratification, risk-adjusted follow-up, and identification of patients with a greater likelihood of response to targeted therapy.