Blood Levels of Carbonic Anhydrase 9 Correlate with Clear Cell Renal Cell Carcinoma Activity

摘要

Introduction Biomarkers for early detection of renal cell carcinoma (RCC) may help diagnose minimal residual disease in patients at risk for RCC, can guide antiangiogenic therapy, or may help identify candidates for adjuvant treatment. In this study, we investigated whether blood levels of carbonic anhydrase 9 (CA9) correlate with RCC tumor burden and therefore disease activity. Methods CA9 is a von Hippel-Lindau-hypoxia inducible factor target upregulated in clear cell RCC. We used an anti-CA9 antibody (M75)-based enzyme-linked immunosorbent assay test to measure CA9 levels in blood obtained before and after nephrectomy for clinically localized disease in patients with: (1) clear cell RCC, (2) papillary and chromophobe RCC or oncocytoma, or (3) benign kidney lesions, and we compared these samples to blood drawn from normal control individuals. Results We observed a significant (p<0.006) decrease in the blood levels of CA9, after nephrectomy for localized disease, in the majority of patients with clear cell RCC (57%). In contrast, patients with nonclear cell RCC, benign disease, or those having undergone debulking nephrectomy for metastatic disease did not have a decrease in CA9 blood levels after nephrectomy. Preliminary longitudinal follow up measurements of CA9 levels in a small group of patients indicated that rising CA9 levels may correlate with disease progression. Conclusions Plasma CA9 levels correlate with disease activity in a subset of clear cell RCC patients and should be considered in future multiplex RCC biomarker development algorithms.