Elevated plasma osteopontin as marker for distant metastases and poor survival in patients with renal cell carcinoma

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Abstract
To evaluate diagnostic and prognostic significance of plasma osteopontin (OPN) in patients with renal cell carcinoma (RCC). The retrospective study included 80 patients with RCC (pN0M0, n = 32; pN1M0, n = 11; M1, and n = 37), and 52 healthy controls (27 females and 25 males). OPN, the bone marker bone-specific alkaline phosphatase (bALP) and carboxyterminal telopetide of type-I collagen (ICTP), and the enzymes alanine aminotransferase (ALAT), and gamma-glutamyltransferase (GGT) were evaluated together with Memorial Sloan-Kettering Cancer Center (MSKCC) laboratory parameters. Data were analyzed by receiver–operating characteristics (ROC), survival analysis, and Cox proportional hazards regression model. OPN and ICTP levels in RCC patients with distant metastases were significantly elevated (medians 115 and 4.7 μg/l, P < 0.001) compared to those without metastases (31.1 and 2.5 μg/l) and controls (28.9 and 2.1 μg/l) but did not differ between patients with bone or non-bone metastases. Both bALP and ALAT were not different between all study groups, while GGT was only increased in patients with non-bone metastases. In ROC analysis, OPN showed the best discrimination between patients with and without metastases (area under the curve: 0.888). High OPN values were associated with poor survival (Kaplan–Meier analysis, log-rank test, P = 0.002). Multivariate Cox regression with forward and backward stepwise elimination confirmed plasma OPN as independent predictive survival factor in RCC patients. Our results show that high plasma OPN levels are associated with distant metastases and poor survival in RCC patients. The use of OPN as potential marker to monitor new treatment strategies in patients with advanced RCC should be evaluated in prospective studies.