背景：肾透明细胞肾癌(KIRC)起源于近曲小管细胞，是肾细胞癌最常见的亚型。KIRC的特点是脂质代谢的改变，而肥胖是其的一个风险因素。C1q和TNF相关蛋白1(C1QTNF1)是一种新型脂肪因子，属于C1q和TNF相关蛋白(CTRP)家族的成员，已被证明对各种癌症的进展有影响。然而，C1QTNF1在KIRC中的作用尚未研究。方法：采用Wilcoxon秩和检验分析KIRC组织和正常组织中C1QTNF1的表达。通过逻辑回归和Wilcoxon秩和检验对临床病理特征与C1QTNF1水平之间的关系进行检查。此外，采用Kaplan-Meier(KM)分析C1QTNF1对KIRC患者预后的影响。使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)对差异基因的潜在信号通路和生物功能进行分析。构建一个用于预测KIRC患者预后的评分系统图。采用Spearman相关分析确定C1QTNF1表达与免疫细胞浸润和免疫检查点基因之间的关系。采用ENCORI在线工具预测C1QTNF1的上游miRNA和lncRNA。最后，我们检测了C1QTNF1敲打后KIRC细胞的增殖、侵袭和迁移能力。结果：KIRC组织中C1QTNF1的表达显著高于正常肾组织。C1QTNF1表达较高的患者预后不良，这一发现得到Kaplan-Meier生存分析的支持。C1QTNF1表达与TNM和病理分期、年龄和性别显著相关(p < 0.05)。C1QTNF1的表达水平与KIRC中免疫细胞浸润和免疫检查点基因显著相关。此外，高C1QTNF1表达与I、II期、T1、T2、T3、T4、N0和M0患者的预后不良相关(HR > 1, p < 0.05)。校准图表明，C1QTNF1模型对KIRC患者的生存预测有较好的效果。C1QTNF1敲打抑制了KIRC细胞的增殖、迁移和侵袭。此外，CYTOR和AC040970.1/hsa-miR-27b-3p轴被鉴定为KIRC中最可能的C1QTNF1上游ncRNA相关通路。结论：总之，我们的研究表明，C1QTNF1的高表达与KIRC的进展和免疫浸润有关。C1QTNF1的表达增加预示着KIRC患者的不良预后。版权所有©2023 Qiu、Wang、Zhao、Zhang、Xu和Xia。

Background: Kidney renal clear cell carcinoma (KIRC) originates from proximal tubular cells and is the most common subtype of renal cell carcinoma. KIRC is characterized by changes in lipid metabolism, and obesity is a risk factor for it. C1q And TNF Related 1 (C1QTNF1), a novel adipokine and member of the C1q and TNF-related protein (CTRP) family, has been shown to affect the progression of various cancers. However, the role of C1QTNF1 in KIRC has not been studied. Methods: The Wilcoxon rank sum test was used to analyze the expression of C1QTNF1 in KIRC tissues and normal tissues. The relationship between clinicopathological features and C1QTNF1 levels was also examined by logistic regression and the Wilcoxon rank sum test. In addition, the effect of C1QTNF1 on the prognosis of KIRC patients was analyzed by Kaplan-Meier (KM). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the potential signaling pathways and biological functions of differential genes. A nomogram was constructed to predict the prognosis of KIRC patients. Spearman correlation analysis was performed to determine the association between C1QTNF1 expression and immune cell infiltration and immune checkpoint genes. The upstream miRNAs and lncRNAs of C1QTNF1 were predicted by the ENCORI online tool. Finally, we examined the proliferation, invasion, and migration abilities of KIRC cells after C1QTNF1 knockdown. Results: The expression of C1QTNF1 in KIRC tissues was significantly higher than in normal renal tissues. Patients with higher C1QTNF1 expression had a poor prognosis, a finding supported by Kaplan-Meier survival analysis. C1QTNF1 expression was significantly correlated with TNM and pathologic stages, age, and gender (p < 0.05). The C1QTNF1 expression level was significantly correlated with immune cell infiltration and immune checkpoint genes in KIRC. Additionally, high C1QTNF1 expression was associated with poor prognosis in stage I and II, T1 and T2, T3 and T4, N0, and M0 patients (HR > 1, p < 0.05). The calibration diagram shows that the C1QTNF1 model has effective predictive performance for the survival of KIRC patients. Knockdown of C1QTNF1 inhibited KIRC cell proliferation, cell migration, and cell invasion. In addition, CYTOR and AC040970.1/hsa-miR-27b-3p axis were identified as the most likely upstream ncRNA-related pathways of C1QTNF1 in KIRC. Conclusion: In conclusion, our study suggests that high expression of C1QTNF1 is associated with KIRC progression and immune infiltration. The increased expression of C1QTNF1 suggests a poor prognosis in KIRC patients.Copyright © 2023 Qiu, Wang, Zhao, Zhang, Xu and Xia.