Landolt Lea, Eikrem Øystein, Strauss Philipp, Scherer Andreas, Lovett David H, Beisland Christian, Finne Kenneth, Osman Tarig, Ibrahim Mohammad M, Gausdal Gro, Ahmed Lavina, Lorens James B, Thiery Jean Paul, Tan Tuan Zea, Sekulic Miroslav, Marti Hans-Peter
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Department of Medicine, Haukeland University Hospital, Bergen, Norway.
Physiol Rep. 2017 Jun;5(11). doi: 10.14814/phy2.13305.
Clear cell renal cell carcinoma (ccRCC) represents the most common type of kidney cancer with high mortality in its advanced stages. Our study aim was to explore the correlation between tumor epithelial-to-mesenchymal transition (EMT) and patient survival. Renal biopsies of tumorous and adjacent nontumorous tissue were taken with a 16 g needle from our patients ( = 26) undergoing partial or radical nephrectomy due to ccRCC RNA sequencing libraries were generated using Illumina TruSeq Access library preparation protocol and TruSeq Small RNA library preparation kit. Next generation sequencing (NGS) was performed on Illumina HiSeq2500. Comparative analysis of matched sample pairs was done using the Bioconductor Limma/voom R-package. Liquid chromatography-tandem mass spectrometry and immunohistochemistry were applied to measure and visualize protein abundance. We detected an increased generic EMT transcript score in ccRCC Gene expression analysis showed augmented abundance of and , as well as down-regulated expression of (klotho). Moreover, microRNA analyses demonstrated a positive expression correlation of miR-34a and its targets and Survival analysis based on a subset of genes from our list EMT-related genes in a publicly available dataset showed that the EMT genes correlated with ccRCC patient survival. Several of these genes also play a known role in fibrosis. Accordingly, recently published classifiers of solid organ fibrosis correctly identified EMT-affected tumor samples and were correlated with patient survival. EMT in ccRCC linked to fibrosis is associated with worse survival and may represent a target for novel therapeutic interventions.
透明细胞肾细胞癌（ccRCC）是最常见的肾癌类型，晚期死亡率很高。我们的研究目的是探讨肿瘤上皮-间质转化（EMT）与患者生存率之间的相关性。从因ccRCC接受部分或根治性肾切除术的患者（n = 26）中，用16g针获取肿瘤组织和相邻非肿瘤组织的肾活检样本。使用Illumina TruSeq Access文库制备方案和TruSeq Small RNA文库制备试剂盒生成RNA测序文库。在Illumina HiSeq2500上进行下一代测序（NGS）。使用Bioconductor Limma/voom R包对匹配样本对进行比较分析。应用液相色谱-串联质谱和免疫组织化学来测量和可视化蛋白质丰度。我们在ccRCC中检测到通用EMT转录本评分增加。基因表达分析显示 和 的丰度增加，以及 （klotho）的表达下调。此外，microRNA分析表明miR-34a与其靶标 和 呈正表达相关性。基于公开可用数据集中我们列出的EMT相关基因子集进行的生存分析表明，EMT基因与ccRCC患者生存率相关。这些基因中的几个在纤维化中也发挥着已知作用。因此，最近发表的实体器官纤维化分类器正确地识别了受EMT影响的肿瘤样本，并与患者生存率相关。ccRCC中与纤维化相关的EMT与较差的生存率相关，可能代表新的治疗干预靶点。
