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

APMIS. 2021 Sep;129(9):535-547. doi: 10.1111/apm.13131. Epub 2021 Jun 30.

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.

Keywords: Hypoxia; hypoxia-inducible factor 1α; predictive marker; prognostic marker.

MeSH terms

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

Substances

  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN127 microRNA, human
  • MicroRNAs
  • SLC2A1 protein, human
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Carbonic Anhydrase IX