ABSTRACT

As the most common histologic subtype of renal cancer, clear cell renal cell carcinoma (ccRCC) poses a serious threat to public health. However, there are no specific molecular-targeted drugs for ccRCC at present. Human ATP-binding cassette (ABC) transporter family plays an important role in homeostasis maintenance. This study aimed to evaluate the potential diagnostic value of ABC genes in ccRCC. A total of 952 samples of ccRCC patients (707) and controls (245) from three different datasets were included for analysis. Receiver operating characteristic analysis and t-test were used to analyze the differential expression of ABC genes in ccRCC patients and control samples at mRNA level during screening and validations. The Cancer Genome Atlas (TCGA-ccRCC) dataset was utilized to investigate the correlation between ABC genes expression and prognostic value in ccRCC. We then investigated the interactions between ABCG1 and proteins in the Comparative Toxicogenomics Database (CTD). Finally, we found that ATP-binding cassette transporter G member 1 (ABCG1) was over-expressed in ccRCC patients compared with healthy samples at mRNA level. Cox regression analysis and Kaplan–Meier analysis showed that ccRCC patients with high ABCG1 expression had better overall survival (OS) than those patients with low expression (hazard ratio (HR) = 0.662, p = 0.007). This study demonstrated that ABCG1 is a potential diagnostic and prognostic biomarker in ccRCC and discussed the molecular mechanisms underlying the relationship between ccRCC and ABCG1, which might provide guidance for better management and treatment of ccRCC in the future.

 抽象的

作为肾癌最常见的组织学亚型，透明细胞肾细胞癌（ccRCC）对公众健康构成严重威胁。但目前尚无针对ccRCC的特异性分子靶向药物。人类 ATP 结合盒 (ABC) 转运蛋白家族在体内平衡维持中发挥着重要作用。本研究旨在评估ABC基因在ccRCC中的潜在诊断价值。来自三个不同数据集的总共 952 个 ccRCC 患者 (707) 和对照 (245) 样本被纳入分析。在筛选和验证过程中，使用受试者操作特征分析和 t 检验来分析 ccRCC 患者和对照样本中ABC基因在 mRNA 水平上的差异表达。利用癌症基因组图谱 (TCGA-ccRCC) 数据集来研究 ccRCC 中 ABC 基因表达与预后价值之间的相关性。然后我们研究了ABCG1和比较毒理学基因组数据库 (CTD) 中蛋白质之间的相互作用。最后，我们发现与健康样本相比，ccRCC 患者中 ATP 结合盒转运蛋白 G 成员 1 ( ABCG1 ) 在 mRNA 水平上过度表达。 Cox回归分析和Kaplan-Meier分析显示ABCG1高表达的ccRCC患者比低表达的患者有更好的总生存期（OS）（风险比（HR）= 0.662， p = 0.007）。本研究证明ABCG1是ccRCC潜在的诊断和预后生物标志物，并讨论了ccRCC和ABCG1之间关系的分子机制，这可能为未来更好地管理和治疗ccRCC提供指导。