Zhou Juntuo, Song Yimeng, Xing Tianying, Ge Liyuan, Ma Lulin, Lu Min, Zhong Lijun
Department of Urology, Peking University Third Hospital, Beijing 100191, China; Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing 100083, China.
Department of Urology, Peking University Third Hospital, Beijing 100191, China.
Transl Oncol. 2021 Jan;14(1):100895. doi: 10.1016/j.tranon.2020.100895. Epub 2020 Oct 6.
Clear cell renal cell carcinoma (ccRCC) is a type of malignant tumor of the urinary system. The renal vein or vena cava thrombus can be found in a subset of ccRCC patients in whom it leads to worse prognosis. However, the protein expression profile and molecular features of ccRCC thrombus remain largely unclear. Here, a comparative proteomic analysis was performed using the 2D-LC-MS strategy for the thrombus-tumor-normal tissue triples of 15 ccRCC patients. Statistical analysis, GO enrichment analysis, protein-protein interaction network construction, and mRNA-based survival analysis were used to interpret the proteomic data. Three dysregulated proteins, GGT5 (gamma-glutamyl transferase 5), KRT7 (keratin 7) and CFHR1 (complement factor H related 1), were analyzed using western blot (WB) and immunohistochemistry (IHC) to validate the reliability of the proteomic analysis. The result of this analysis revealed 251 dysregulated proteins, which could be divided into 11 clusters depending on the changing trends, among the thrombus, tumor, and normal tissues. Several pathways and regulation networks were found to be associated with the thrombus, and some dysregulated proteins showed potential values for prognosis prediction. WB and IHC results were in accordance with the proteomic results, further validating the reliability of this study. In conclusion, our findings provide an overview of the thrombus at the molecular level as well as valuable information for further pathological studies or research on biomarkers and therapeutic targets.
透明细胞肾细胞癌（ccRCC）是泌尿系统的一种恶性肿瘤。在一部分ccRCC患者中可发现肾静脉或腔静脉血栓，这会导致更差的预后。然而，ccRCC血栓的蛋白质表达谱和分子特征仍 largely不清楚。在此，使用二维液相色谱-质谱联用（2D-LC-MS）策略对15例ccRCC患者的血栓-肿瘤-正常组织三联样本进行了比较蛋白质组学分析。采用统计分析、基因本体（GO）富集分析、蛋白质-蛋白质相互作用网络构建和基于mRNA的生存分析来解释蛋白质组学数据。使用蛋白质免疫印迹（WB）和免疫组织化学（IHC）对三种失调蛋白，即γ-谷氨酰转移酶5（GGT5）、角蛋白7（KRT7）和补体因子H相关蛋白1（CFHR1）进行分析，以验证蛋白质组学分析的可靠性。该分析结果显示，在血栓、肿瘤和正常组织中，有251种失调蛋白，根据其变化趋势可分为11个簇。发现了一些与血栓相关的信号通路和调控网络，一些失调蛋白显示出预后预测的潜在价值。WB和IHC结果与蛋白质组学结果一致，进一步验证了本研究的可靠性。总之，我们的研究结果在分子水平上提供了血栓的概况，以及为进一步的病理学研究或生物标志物和治疗靶点研究提供了有价值的信息。
