Clear-cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy. The pathogenesis of the disease is currently poorly understood, and the prognosis is poor. Therefore, in this study, we focused on exploring and identifying genes and signal transduction pathways that are closely related to ccRCC. Differentially expressed genes (DEGs) were analyzed using the renal cell oncogene expression profiles GSE100666 and GSE68417. DAVID evaluation of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses was used. We constructed a protein–protein interaction (PPI) network of DEGS using Cytoscape software and analyzed the submodules with the CytoHubba plugin. Finally, we performed western blot, immunohistochemistry, and PCR validation by collecting tissues, and also utilized cells for in vitro functional analysis of ceruloplasmin (CP). In total, 202 DEGs (52 upregulated and 150 downregulated genes) were identified. Upregulated DEGs are significantly rich in angiogenesis, cell adhesion, and response to hypoxia, whereas downregulated DEGs are involved in intracellular pH regulation, excretion, coagulation, and chloride transmembrane transport. We selected the interactions of the top 20 hub genes provided by the PPI network, all of which are involved in important physiological pathways in vivo, such as complement and coagulation cascades. Tissue protein assays demonstrated that renal cancer highly expressed CP, while in vitro experiments showed that CP could promote the invasion of renal cancer cells. Our study suggests that ALB, C3, LOX, HRG, CXCR4, GPC3, SLC12A3, CP, and CASR may be involved in the development of ccRCC, and is expected to provide theoretical support for future studies on the diagnosis and targeted therapy of ccRCC.

中文翻译：

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铜蓝蛋白过表达与透明细胞肾细胞癌的致癌途径和较差的存活率有关

透明细胞肾细胞癌 (ccRCC) 是最常见的肾脏恶性肿瘤。目前对该病的发病机制知之甚少，预后较差。因此，在本研究中，我们重点探索和鉴定与ccRCC密切相关的基因和信号转导通路。使用肾细胞癌基因表达谱 GSE100666 和 GSE68417 分析差异表达基因 (DEG)。使用了基因本体论 (GO) 的 DAVID 评估和京都基因和基因组百科全书 (KEGG) 分析。我们使用 Cytoscape 软件构建了 DEGS 的蛋白质-蛋白质相互作用 (PPI) 网络，并使用 CytoHubba 插件分析了子模块。最后，我们通过收集组织进行了蛋白质印迹、免疫组织化学和 PCR 验证，并将细胞用于体外铜蓝蛋白（CP）的功能分析。总共鉴定了 202 个 DEG（52 个上调基因和 150 个下调基因）。上调的 DEG 显着丰富血管生成、细胞粘附和对缺氧的反应，而下调的 DEG 参与细胞内 pH 调节、排泄、凝血和氯化物跨膜转运。我们选择了 PPI 网络提供的前 20 个中枢基因的相互作用，所有这些基因都参与了体内重要的生理途径，例如补体和凝血级联。组织蛋白测定表明肾癌高表达 CP，而在体外实验表明，CP可以促进肾癌细胞的侵袭。我们的研究提示ALB、C3、LOX、HRG、CXCR4、GPC3、SLC12A3、CP和CASR可能参与了ccRCC的发生发展，有望为未来ccRCC的诊断和靶向治疗研究提供理论支持。