Department of Urology, University Hospital Bonn, Bonn, Germany.
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Eur Urol Focus. 2021 Sep;7(5):1121-1129. doi: 10.1016/j.euf.2020.09.007. Epub 2020 Oct 1.
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.
DESIGN, SETTING, AND PARTICIPANTS: 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.
ATP 结合盒（ABC）转运蛋白在多种癌症实体的多药耐药发展中起着至关重要的作用。
我们的研究旨在使用癌症基因组图谱（TCGA）数据集全面分析肾细胞癌（RCC）中的 ABC 亚家族 B（ABCB）。
设计、设置和参与者：我们对 TCGA 数据集用于透明细胞、乳头状和嫌色 RCC 的 ABCB1-10 进行了系统的生存分析。
通过包含 152 个样本的透明细胞 RCC（ccRCC）队列中的定量聚合酶链反应验证了结果。随后，通过免疫组织化学和随后的定量图像分析，在包含 144 个样本的组织微阵列 RCC 队列中评估了 ABCB8 蛋白表达。在体外，ACHN 和 CAKI1 中的反义寡核苷酸诱导的 ABCB8 敲低在功能分析后建立。
各种 ABCB 成员在三种最常见的 RCC 亚型中具有预后价值。值得注意的是，ABCB8 被确定为 RCC TCGA 队列中最具预后的 ABCB 基因。此外，ABCB8 被证明是三个独立队列中缩短癌症特异性生存的独立预测因子。在体外，特异性 ABCB8 敲低降低了 ACHN 和 CAKI1 的活力和迁移能力。
ABCB8 被确定为有前途的预后生物标志物。功能分析表明 ABCB8 在 ccRCC 中具有促进肿瘤的作用。
在这项研究中，转运蛋白基因 ABCB8 被证明是透明细胞肾细胞癌更差临床病程的风险预测因子。在肾癌细胞培养模型中，该基因的耗竭导致恶性潜能降低，因此抑制该基因可能具有治疗价值。
