Blood levels of carbonic anhydrase 9 correlate with clear cell renal cell carcinoma activity

Peter Hulick, Michael Zimmer, Vitaly Margulis, Steven Skates, Maureen Hamel, Douglas M. Dahl, Dror M. Michaelson, Towia Liebermann, Sabina Signoretti, Walter Carney, Christopher Wood, Othon Iliopoulos

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)37-45
Number of pages9
JournalClinical Proteomics
Volume5
Issue number1
DOIs
StatePublished - Mar 2009

Fingerprint

Carbonic Anhydrases
Renal Cell Carcinoma
Blood
Cells
Nephrectomy
Biomarkers
Carbonic Anhydrase IX
Immunosorbents
Residual Neoplasm
Tumors
Assays
Tumor Burden
Disease Progression
Plasmas
Enzyme-Linked Immunosorbent Assay
Antibodies
Kidney

Keywords

  • Angiogenesis
  • Carbonic anhydrase 9
  • Circulating biomarker
  • Hypoxia inducible factor
  • Renal cell carcinoma
  • VHL

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

Cite this

Blood levels of carbonic anhydrase 9 correlate with clear cell renal cell carcinoma activity. / Hulick, Peter; Zimmer, Michael; Margulis, Vitaly; Skates, Steven; Hamel, Maureen; Dahl, Douglas M.; Michaelson, Dror M.; Liebermann, Towia; Signoretti, Sabina; Carney, Walter; Wood, Christopher; Iliopoulos, Othon.

In: Clinical Proteomics, Vol. 5, No. 1, 03.2009, p. 37-45.

Research output: Contribution to journalArticle

Hulick, P, Zimmer, M, Margulis, V, Skates, S, Hamel, M, Dahl, DM, Michaelson, DM, Liebermann, T, Signoretti, S, Carney, W, Wood, C & Iliopoulos, O 2009, 'Blood levels of carbonic anhydrase 9 correlate with clear cell renal cell carcinoma activity', Clinical Proteomics, vol. 5, no. 1, pp. 37-45. https://doi.org/10.1007/s12014-008-9012-1
Hulick, Peter ; Zimmer, Michael ; Margulis, Vitaly ; Skates, Steven ; Hamel, Maureen ; Dahl, Douglas M. ; Michaelson, Dror M. ; Liebermann, Towia ; Signoretti, Sabina ; Carney, Walter ; Wood, Christopher ; Iliopoulos, Othon. / Blood levels of carbonic anhydrase 9 correlate with clear cell renal cell carcinoma activity. In: Clinical Proteomics. 2009 ; Vol. 5, No. 1. pp. 37-45.
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AU - Dahl, Douglas M.

AU - Michaelson, Dror M.

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AB - 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.

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