Comprehensive Analysis of the ATP-binding Cassette Subfamily B Across Renal Cancers Identifies ABCB8 Overexpression in Phenotypically Aggressive Clear Cell Renal Cell Carcinoma.
ABCB8
ATP-binding cassette subfamily B
Clear cell renal cell carcinoma
Malignant phenotype
Renal cell carcinoma
Journal
European urology focus
ISSN: 2405-4569
Titre abrégé: Eur Urol Focus
Pays: Netherlands
ID NLM: 101665661
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
18
03
2020
revised:
24
07
2020
accepted:
16
09
2020
pubmed:
5
10
2020
medline:
14
4
2022
entrez:
4
10
2020
Statut:
ppublish
Résumé
ATP-binding cassette (ABC) transporters play a crucial role in the development of multidrug resistance in diverse cancer entities. Our study was designed to comprehensively analyze the ABC subfamily B (ABCB) in renal cell carcinoma (RCC) using The Cancer Genome Atlas (TCGA) datasets. We performed systematic survival analyses of ABCB1-10 using the TCGA datasets for clear cell, papillary, and chromophobe RCC. Results were validated via quantitative polymerase chain reaction in a clear cell RCC (ccRCC) cohort containing 152 samples. Afterward, ABCB8 protein expression was assessed in a tissue microarray RCC cohort (n = 144) by immunohistochemistry with subsequent quantitative image analysis. In vitro, antisense oligonucleotide-induced ABCB8 knockdowns were established in ACHN and CAKI1 following functional analyses. Various ABCB members have prognostic value among the three most occurring RCC subtypes. Of note, ABCB8 was identified as the most prognostic ABCB gene in the RCC TCGA cohorts. Further, ABCB8 proved to be an independent predictor of shortened cancer-specific survival in three independent cohorts. In vitro, specific ABCB8 knockdown reduced viability and migration capacity in ACHN and CAKI1. ABCB8 was identified as a promising prognostic biomarker. Functional analyses suggest a tumor-promoting role of ABCB8 in ccRCC. In this study, the transporter gene ABCB8 proved to be a risk predictor of a worse clinical course in clear cell renal cell carcinoma. In the renal cell carcinoma cell culture model, depletion of this gene led to a reduction in the malignant potential, and inhibition of this gene may therefore possess a therapeutic value.
Sections du résumé
BACKGROUND
BACKGROUND
ATP-binding cassette (ABC) transporters play a crucial role in the development of multidrug resistance in diverse cancer entities.
OBJECTIVE
OBJECTIVE
Our study was designed to comprehensively analyze the ABC subfamily B (ABCB) in renal cell carcinoma (RCC) using The Cancer Genome Atlas (TCGA) datasets.
DESIGN, SETTING, AND PARTICIPANTS
METHODS
We performed systematic survival analyses of ABCB1-10 using the TCGA datasets for clear cell, papillary, and chromophobe RCC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
METHODS
Results were validated via quantitative polymerase chain reaction in a clear cell RCC (ccRCC) cohort containing 152 samples. Afterward, ABCB8 protein expression was assessed in a tissue microarray RCC cohort (n = 144) by immunohistochemistry with subsequent quantitative image analysis. In vitro, antisense oligonucleotide-induced ABCB8 knockdowns were established in ACHN and CAKI1 following functional analyses.
RESULTS AND LIMITATIONS
CONCLUSIONS
Various ABCB members have prognostic value among the three most occurring RCC subtypes. Of note, ABCB8 was identified as the most prognostic ABCB gene in the RCC TCGA cohorts. Further, ABCB8 proved to be an independent predictor of shortened cancer-specific survival in three independent cohorts. In vitro, specific ABCB8 knockdown reduced viability and migration capacity in ACHN and CAKI1.
CONCLUSIONS
CONCLUSIONS
ABCB8 was identified as a promising prognostic biomarker. Functional analyses suggest a tumor-promoting role of ABCB8 in ccRCC.
PATIENT SUMMARY
RESULTS
In this study, the transporter gene ABCB8 proved to be a risk predictor of a worse clinical course in clear cell renal cell carcinoma. In the renal cell carcinoma cell culture model, depletion of this gene led to a reduction in the malignant potential, and inhibition of this gene may therefore possess a therapeutic value.
Identifiants
pubmed: 33011150
pii: S2405-4569(20)30266-2
doi: 10.1016/j.euf.2020.09.007
pii:
doi:
Substances chimiques
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1121-1129Informations de copyright
Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.