hERG1 and CA IX expression are associated with disease recurrence in surgically resected clear cell renal carcinoma.
Aged
Biomarkers, Tumor
/ metabolism
Carbonic Anhydrase IX
/ metabolism
Carcinoma, Renal Cell
/ metabolism
Ether-A-Go-Go Potassium Channels
/ metabolism
Female
Humans
Italy
Kidney Neoplasms
/ metabolism
Male
Middle Aged
Neoplasm Recurrence, Local
/ metabolism
Neoplasm Staging
Nephrectomy
/ methods
Prognosis
Survival Rate
CA IX
Multiprotein complex
Prognosis
Renal tumours
hERG1
Journal
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
ISSN: 1532-2157
Titre abrégé: Eur J Surg Oncol
Pays: England
ID NLM: 8504356
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
15
08
2019
revised:
22
10
2019
accepted:
25
10
2019
pubmed:
5
11
2019
medline:
23
7
2020
entrez:
5
11
2019
Statut:
ppublish
Résumé
In search of novel prognostic biomarkers for clear cell renal carcinoma (ccRCC), we analysed the expression of several proteins related to angiogenesis and hypoxia. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31679954
pii: S0748-7983(19)30911-4
doi: 10.1016/j.ejso.2019.10.031
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Ether-A-Go-Go Potassium Channels
0
KCNH1 protein, human
0
Carbonic Anhydrase IX
EC 4.2.1.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
209-215Informations de copyright
Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.