Prognostic value of copper transporter 1 expression in patients with clear cell renal cell carcinoma.

Abstract

Clear cell renal cell carcinoma (ccRCC) features a Von Hippel-Lindau mutation, associated with a hypoxia-inducible factor (HIF) imbalance. Copper transporter 1 (CTR1) may also promote tumor progression through the modulation of the HIF pathway by copper. Therefore, the present study explored the prognostic effect of tumor CTR1 expression in patients with ccRCC. A total of 293 patients with ccRCC that underwent nephrectomy were retrospectively enrolled. CTR1 expression was assessed by immunohistochemistry, and its association with clinicopathological features and prognosis were evaluated. The present data indicated that high tumor CTR1 expression was independently associated with poor overall survival (OS) [hazard ratio, 2.291; 95% confidence interval (CI), 1.389–3.777; P<0.001] and disease-free survival (DFS) (hazard ratio, 2.210; 95% CI, 1.299–3.759; P=0.003) rates in patients with ccRCC. Furthermore, CTR1 expression was significantly higher for Mayo Clinic stage, size, grade and necrosis score risk groups, and could be incorporated into several existing prognostic models to improve performance. Nomograms incorporating tumor CTR1 expression with other parameters performed well in the 5- and 8-year OS and DFS rate predictions of patients (concordance index 0.805 and 0.787, respectively). In conclusion, the present study demonstrated that CTR1 expression is a potential independent biomarker for poor prognosis for the recurrence and survival prediction of patients with ccRCC following nephrectomy.