hERG1 and CA IX expression are associated with disease recurrence in surgically resected clear cell renal carcinoma

Eur J Surg Oncol. 2020 Jan;46(1):209-215. doi: 10.1016/j.ejso.2019.10.031. Epub 2019 Oct 31.

Abstract

Background: In search of novel prognostic biomarkers for clear cell renal carcinoma (ccRCC), we analysed the expression of several proteins related to angiogenesis and hypoxia.

Methods: A monocentric study on 30 consecutive surgical samples from surgically-treated ccRCC patients with a 10-year follow up was performed. The following proteins were analysed by immunohistochemistry: Vascular Endothelial Growth Factor- A (VEGF-A), Platelet-Derived Growth Factor β Receptor (PDGFRβ), VEGF-receptor 1 (Flt1), VEGF-receptor 2 (KDR), Glucose Transporter 1 (GLUT1), Carbonic anhydrase IX (CA-IX) and the hERG1 potassium channel. Data were analysed in conjunction with the clinico-pathological characteristics of the patients and follow up.

Results: All the proteins were expressed in the samples, with statistically significant associations of VEGF-A with PDGFRβ and Flt1 and hERG1 with CA IX. Notably, hERG1 and CAIX co-immunoprecipitated in primary ccRCC samples and survival analysis showed that the positivity for hERG1 and CA IX had a negative impact on Recurrence Free Survival (RFS) at the univariate analysis. At the multivariate analysis only hERG1 maintained its statistically significant negative impact.

Conclusions: hERG1 expression can be exploited to predict recurrence in surgically-treated ccRCC patients. hERG1 channels form a multiprotein complex with the pH regulator CA IX in primary ccRCC samples their potential use as therapeutic target might be suggested.

Keywords: CA IX; Multiprotein complex; Prognosis; Renal tumours; hERG1.

MeSH terms

  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrase IX / metabolism*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery*
  • Ether-A-Go-Go Potassium Channels / metabolism*
  • Female
  • Humans
  • Italien
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Staging
  • Nephrectomy / methods
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Ether-A-Go-Go Potassium Channels
  • KCNH1 protein, human
  • Carbonic Anhydrase IX