Iulia Blajan1, Herdis Miersch1, Doris Schmidt1, Glen Kristiansen2, Sven Perner3, Manuel Ritter1, Jörg Ellinger1, Niklas Klümper4. 1. Department of Urology, University Hospital Bonn, Bonn, Germany. 2. Institute of Pathology, University Hospital Bonn, Bonn, Germany. 3. Institute of Pathology, University of Luebeck and University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany; Pathology, Research Center Borstel, Leibniz Lung Center, Borstel, Germany. 4. Department of Urology, University Hospital Bonn, Bonn, Germany; Institute of Experimental Oncology, University Hospital Bonn, Bonn, Germany. Electronic address: niklas.kluemper@ukbonn.de.
Abstract
BACKGROUND: ATP-binding cassette (ABC) transporters play a crucial role in the development of multidrug resistance in diverse cancer entities. 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: We performed systematic survival analyses of ABCB1-10 using the TCGA datasets for clear cell, papillary, and chromophobe RCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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: 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: ABCB8 was identified as a promising prognostic biomarker. Functional analyses suggest a tumor-promoting role of ABCB8 in ccRCC. PATIENT SUMMARY: 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.
BACKGROUND: ATP-binding cassette (ABC) transporters play a crucial role in the development of multidrug resistance in diverse cancer entities. 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: We performed systematic survival analyses of ABCB1-10 using the TCGA datasets for clear cell, papillary, and chromophobe RCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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: 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: ABCB8 was identified as a promising prognostic biomarker. Functional analyses suggest a tumor-promoting role of ABCB8 in ccRCC. PATIENT SUMMARY: 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.