背景：肾透明细胞癌（KIRC）是肾细胞癌（RCC）的一个代表性组织学亚型。RCC表现出强烈的免疫原性，并有显著的免疫细胞浸润功能不全。亮型补体C1q C链（C1QC）是血清亮型补体系统中的多肽，参与肿瘤发生和调节肿瘤微环境（TME）。然而，研究尚未探讨C1QC表达对KIRC预后和肿瘤免疫的影响。 方法：使用TIMER和TCGA门户网站数据库检测了广泛的肿瘤组织和正常组织在C1QC表达方面的差异，并通过Human Protein Atlas进一步验证了C1QC蛋白表达。然后，采用UALCAN数据库研究了C1QC表达与临床病理数据和其他基因的关联。随后，通过查询Kaplan-Meier绘图器数据库预测了C1QC表达与预后的关联。使用STRING软件和Metascape数据库建立了蛋白质-蛋白质相互作用（PPI）网络，以便深入研究C1QC功能的机制。TISCH数据库协助评估了单个细胞水平的不同细胞类型中的C1QC表达。此外，使用TIMER平台评估了C1QC和肿瘤免疫细胞浸润水平的关联。选择TISIDB网站深入研究C1QC与免疫调节因子表达的Spearman相关性。最后，使用沉默策略评估了C1QC如何影响体外细胞增殖、迁移和侵袭。 结果：KIRC组织与相邻正常组织相比，C1QC水平明显上调，与肿瘤分期、分级和淋巴结转移呈正相关，在KIRC的临床预后方面呈负相关。体外实验结果显示，C1QC沉默抑制了KIRC细胞的增殖、迁移和侵袭。此外，功能和通路富集分析表明，C1QC参与免疫系统相关的生物过程。根据单细胞RNA分析，C1QC在巨噬细胞群中表现出特异性上调。此外，在KIRC中，C1QC与各种肿瘤浸润免疫细胞存在明显的关联。此外，在KIRC的不同免疫细胞子集中，高C1QC表达呈不一致的预后。免疫因子可能对KIRC中的C1QC功能起贡献。 结论：C1QC有资格从生物学角度预测KIRC预后和免疫浸润。针对C1QC可能为KIRC的治疗带来新的希望。版权所有©2023 Yao，Liu，Xu，Cai，Hang，Lu，Zhao，Yang和Zong。

Background: Kidney renal clear cell carcinoma (KIRC) is a representative histologic subtype of renal cell carcinoma (RCC). RCC exhibits a strong immunogenicity with a prominent dysfunctional immune infiltration. Complement C1q C chain (C1QC) is a polypeptide in serum complement system and is involved in tumorigenesis and the modulation of tumor microenvironment (TME). However, researches have not explored the effect of C1QC expression on prognosis and tumor immunity of KIRC. Methods: The difference in a wide variety of tumor tissues and normal tissues in terms of the C1QC expression was detected using TIMER and TCGA portal databases, and further validation of protein expression of C1QC was conducted via Human Protein Atlas. Then, the associations of C1QC expression with clinicopathological data and other genes were studied with the use of UALCAN database. Subsequently, the association of C1QC expression with prognosis was predicted by searching the Kaplan-Meier plotter database. A protein-protein interaction (PPI) network with the Metascape database was built using STRING software, such that the mechanism underlying the C1QC function can be studied in depth. The TISCH database assisted in the evaluation of C1QC expression in different cell types in KIRC at the single-cell level. Moreover, the association of C1QC and the infiltration level of tumor immune cell was assessed using TIMER platform. The TISIDB website was selected to deeply investigate the Spearman correlation between C1QC and immune-modulator expression. Lastly, how C1QC affected the cell proliferation, migration, and invasion in vitro was assessed using knockdown strategies. Results: KIRC tissues had notably upregulated C1QC level in comparison with adjacent normal tissues, with showed a positive relevance to clinicopathological features including tumor stage, grade, and nodal metastasis, and a negative relevance to clinical prognosis in KIRC. C1QC knockdown inhibited KIRC cell proliferation, migration, and invasion, as indicated by the results of the in vitro experiment. Furthermore, functional and pathway enrichment analysis demonstrated that C1QC was involved in immune system-related biological processes. According to single-cell RNA analysis, C1QC exhibited a specific upregulation in macrophages cluster. Additionally, there was an obvious association of C1QC and a wide variety of tumor-infiltrating immune cells in KIRC. Also, high C1QC expression presented inconsistent prognosis in different enriched immune cells subgroups in KIRC. Immune factors might contribute to C1QC function in KIRC. Conclusion: C1QC is qualified to predict KIRC prognosis and immune infiltration biologically. Targeting C1QC may bring new hope for the treatment of KIRC.Copyright © 2023 Yao, Liu, Xu, Cai, Hang, Lu, Zhao, Yang and Zong.