Department of Urology, Hexi University Affiliated Zhangye People's Hospital, Gansu, China.
Institute of Urology, Hexi University, Zhangye Gansu, China.
Int J Biol Markers. 2023 Jun;38(2):124-132. doi: 10.1177/03936155231161366. Epub 2023 Mar 7.
Complement C5a is an important component of the innate immune system. An increasing number of reports have revealed the relevance of C5a in tumor progression; however, its exact role in metastatic renal cell carcinoma (mRCC) remains unknown.
We evaluated C5a expression in tumor tissue microarrays of 231 mRCC patients and analyzed the relationship between C5a levels and clinical outcomes, and the expression of epithelial-mesenchymal transition (EMT)-related proteins, programmed cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). In-vitro functional experiments using exogenous C5a stimulation and C5a silencing in renal cell carcinoma cells were used to validate the tissue findings.
High C5a expression was associated with poor therapeutic responses, poor overall and progression-free survival, and high expression of EMT-related proteins and PD-1/PD-L1 in mRCC patients. Exogenous C5a promoted proliferation, migration, and invasion of renal cell carcinoma cells, and induced the expression of EMT-related proteins and PD-1/PD-L1. Conversely, C5a silencing inhibited migration and invasion of renal cell carcinoma cells and decreased the expression of EMT-related proteins and PD-1/PD-L1.
Our findings indicate that elevated C5a expression is associated with poor outcomes in patients with mRCC, and this effect may be partly attributed to the ability of C5a to promote EMT and PD-1/PD-L1 expression. C5a may be a potential novel target for the treatment of mRCC.
补体 C5a 是先天免疫系统的重要组成部分。越来越多的报告揭示了 C5a 在肿瘤进展中的相关性；然而，其在转移性肾细胞癌（mRCC）中的确切作用仍不清楚。
我们评估了 231 例 mRCC 患者肿瘤组织微阵列中 C5a 的表达，并分析了 C5a 水平与临床结局之间的关系，以及上皮-间充质转化（EMT）相关蛋白、程序性细胞死亡蛋白 1（PD-1）和程序性细胞死亡配体 1（PD-L1）的表达。使用外源性 C5a 刺激和肾癌细胞中的 C5a 沉默进行体外功能实验，以验证组织发现。
高 C5a 表达与 mRCC 患者治疗反应差、总生存期和无进展生存期差以及 EMT 相关蛋白和 PD-1/PD-L1 表达高相关。外源性 C5a 促进肾癌细胞的增殖、迁移和侵袭，并诱导 EMT 相关蛋白和 PD-1/PD-L1 的表达。相反，C5a 沉默抑制肾癌细胞的迁移和侵袭，并降低 EMT 相关蛋白和 PD-1/PD-L1 的表达。
我们的研究结果表明，mRCC 患者中 C5a 表达升高与不良预后相关，这种作用可能部分归因于 C5a 促进 EMT 和 PD-1/PD-L1 表达的能力。C5a 可能是治疗 mRCC 的一个潜在新靶点。
