Recent advancements in proteomics have enhanced our understanding of clear cell renal cell carcinoma (CCRCC). Utilizing a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) followed by immunohistochemical validation, we investigated the expression levels of UCHL1, PAK4, and SNRNP200 in high-grade CCRCC samples. Our analysis also integrated Reactome pathway enrichment to elucidate the roles of these proteins in cancer-related pathways. Our results revealed significant upregulation of UCHL1 and SNRNP200 and downregulation of PAK4 in high-grade CCRCC tissues compared to non-cancerous tissues. UCHL1, a member of the ubiquitin carboxy-terminal hydrolase family, showed variable expression across different tissues and was notably involved in the Akt signaling pathway, which plays a critical role in cellular survival in various cancers. SNRNP200, a key component of the RNA splicing machinery, was found to be essential for proper cell cycle progression and possibly linked to autosomal dominant retinitis pigmentosa. PAK4’s role was noted as critical in RCC cell proliferation and invasion and its expression correlated significantly with poor progression-free survival in CCRCC. Additionally, the expression patterns of these proteins suggested potential as prognostic markers for aggressive disease phenotypes. This study confirms the upregulation of UCHL1, SNRNP200, and PAK4 as significant factors in the progression of high-grade CCRCC, linking their enhanced expression to poor clinical outcomes. These findings propose these proteins as potential prognostic markers and therapeutic targets in CCRCC, offering novel insights into the molecular landscape of this malignancy and highlighting the importance of targeted therapeutic interventions.
蛋白质组学的最新进展加深了我们对透明细胞肾细胞癌（CCRCC）的认识。本研究结合液相色谱-串联质谱（LC-MS/MS）与免疫组化验证技术，检测了高级别CCRCC样本中UCHL1、PAK4和SNRNP200的表达水平，并通过Reactome通路富集分析阐明这些蛋白在癌症相关通路中的作用。结果显示，与癌旁组织相比，高级别CCRCC组织中UCHL1和SNRNP200显著上调，而PAK4表达下调。作为泛素羧基末端水解酶家族成员，UCHL1在不同组织中表达存在差异，并显著参与Akt信号通路——该通路在多种癌症的细胞存活中起关键作用。SNRNP200作为RNA剪接机制的核心组分，被发现对正常细胞周期进程至关重要，并可能与常染色体显性视网膜色素变性相关。PAK4在肾细胞癌增殖和侵袭中发挥关键作用，其表达水平与CCRCC患者较短的无进展生存期显著相关。此外，这些蛋白的表达模式提示其可能作为侵袭性表型疾病的预后标志物。本研究证实UCHL1、SNRNP200和PAK4的上调是高级别CCRCC进展的重要因素，其高表达与不良临床结局相关。这些发现提示这些蛋白可作为CCRCC潜在的预后标志物和治疗靶点，为该恶性肿瘤的分子机制研究提供了新见解，并凸显了靶向治疗干预的重要性。
肿瘤(癌症)患者之家