Nephrology Xagena

Clear cell renal cell carcinoma: decreased expression of CTR2 predicts poor prognosis

Clear cell renal cell carcinoma ( ccRCC ) is well known for its hypervascularity due to the Von Hippel-Lindau/hypoxia-inducible factor dysregulation.
Recent findings suggested that copper transporter 2 ( CTR2 ) is also associated with angiogenesis through copper׳s modulation of the hypoxia-inducible factor pathway.

Researchers have explored the prognostic role of CTR2 in patients with clear cell renal cell carcinoma.

A total of 331 patients with clear cell renal cell carcinoma who underwent nephrectomy were enrolled during 2005-2007 period at a single institution.

The median follow-up was 98.97 months ( 2.63–120.47 ).

Patients׳ samples were collected and stained for CTR2 by immunohistochemistry.

CTR2 expression in clear cell renal cell carcinoma was decreased compared with that in the peritumoral tissue ( P less than 0.001 ) and negatively correlated with many other clinical parameters.

In survival analyses using the Kaplan-Meier method, low tumoral CTR2 expression displayed a dismal prognostic effect both in overall survival and disease-free survival prediction ( P less than 0.001 ).

Multivariate analyses also revealed the same result after adjusted with other clinical parameters ( P less than 0.001 ).

Stratifying patients into 3 risk levels using the Stage, Size, Grade, and Necrosis score and University of California Los Angeles Integrated Staging System score, decreased CTR2 expression associated with shorter overall survival and disease-free survival in the low- and intermediate-risk groups.

Moreover, the generated nomogram integrating tumoral CTR2 expression performed better in predicting patients׳ overall survival than using TNM stages alone ( c-index = 0.799; 95% CI: 0.752–0.846 vs 0.691; 95% CI: 0.637–0.745 ).

In conclusion, CTR2 is a novel prognostic marker for patients with clear cell renal cell carcinoma both in overall survival and disease-free survival prediction, and could be incorporated with other clinical parameters for better patient risk stratification. ( Xagena )

Xia Y et al, Urol Oncol 2016; 34: 5.e1–5.e9