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

Clinical Proteomics

Towia Liebermann⁴  Vitaly Margulis⁶  Dror M. Michaelson⁵  Michael Zimmer⁵  Douglas M. Dahl⁷  Othon Iliopoulos⁵  Peter Hulick⁵  Sabina Signoretti¹  Steven Skates²  Walter Carney³  Christopher Wood⁶  Maureen Hamel⁵ 

[1] Department of Pathology, Brigham and Women’s Hospital, Boston, USADepartment of Pathology, Brigham and Women’s Hospital, Boston, USADepartment of Pathology, Brigham and Women’s Hospital, Boston, USA;Department of Biostatistics, Massachusetts General Hospital, Boston, USADepartment of Biostatistics, Massachusetts General Hospital, Boston, USADepartment of Biostatistics, Massachusetts General Hospital, Boston, USA;Siemens Diagnostics Inc., Boston, USASiemens Diagnostics Inc., Boston, USASiemens Diagnostics Inc., Boston, USA;Beth Israel Deaconess Medical Center, Boston, USABeth Israel Deaconess Medical Center, Boston, USABeth Israel Deaconess Medical Center, Boston, USA;Massachusetts General Hospital Cancer Center, Boston, USAMassachusetts General Hospital Cancer Center, Boston, USAMassachusetts General Hospital Cancer Center, Boston, USA;Department of Urology, MD Anderson Cancer Center, Houston, USADepartment of Urology, MD Anderson Cancer Center, Houston, USADepartment of Urology, MD Anderson Cancer Center, Houston, USA;Department of Urology, Massachusetts General Hospital, Boston, USADepartment of Urology, Massachusetts General Hospital, Boston, USADepartment of Urology, Massachusetts General Hospital, Boston, USA

关键词: Renal cell carcinoma;    Circulating biomarker;    VHL;    Carbonic anhydrase 9;    Angiogenesis;    Hypoxia inducible factor;   

DOI  :  10.1007/s12014-008-9012-1

来源: Humana Press Inc

【 摘 要 】

Abstract

Introduction

Biomarkers for early detection of renal cell carcinoma (RCC) may help diagnose minimal residual disease in patients at risk for RCC, can guide anti-angiogenic 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.

【 授权许可】

Unknown