Surgically induced ischemia has no impact on protein expression levels of HIF-1α and related biomarkers in renal cell carcinoma

Minne Line Mikkelsen, Niels Marcussen, Maj Rabjerg*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

The increasing demands for personalized targeted therapy directed against renal cell carcinoma have driven a search for predictive markers. Novel therapies targeting HIF-1α in renal cell carcinoma have been developed, and HIF-1α has been suggested as a novel predictive marker of response to therapy. The surgical resection of a kidney tumor induces tissue ischemia, and HIF-1α is an oxygen-sensitive transcription factor, which is known to be upregulated during hypoxia. This study investigated the impact of intra-surgical and post-surgical ischemia on protein expression levels of HIF-1α and three related biomarkers (VEGF, GLUT-1, and CAIX) in 20 patients with renal cell carcinoma with immunohistochemistry and Western blotting. Surgical ischemia did not have a significant impact on protein expression levels of any of the investigated markers. Long-post-surgical ischemia resulted in reduced expression levels of HIF-1α, probably due to autolysis. Our results suggest that HIF-1α is a stable protein, with expression levels not affected by intra-surgical ischemia, and hence, HIF-1α is suited for marker analysis.

Original languageEnglish
JournalAPMIS
Volume129
Issue number9
Pages (from-to)535-547
ISSN0903-4641
DOIs
Publication statusPublished - Sep 2021

Keywords

  • Hypoxia
  • hypoxia-inducible factor 1α
  • predictive marker
  • prognostic marker
  • Ischemia/genetics
  • MicroRNAs/genetics
  • Tumor Hypoxia/genetics
  • Prognosis
  • Prospective Studies
  • Tissue Array Analysis
  • Humans
  • Middle Aged
  • Male
  • Vascular Endothelial Growth Factor A/metabolism
  • Carcinoma, Renal Cell/blood supply
  • Kidney Neoplasms/blood supply
  • Nephrectomy
  • Aged, 80 and over
  • Female
  • Aged
  • Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
  • Biomarkers, Tumor/metabolism
  • Glucose Transporter Type 1/metabolism
  • Carbonic Anhydrase IX/metabolism

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