芳香犬尿氨酸甲酰胺酶 (AFMID) 是一种参与色氨酸途径的酶，将 N-甲酰犬尿氨酸代谢为犬尿氨酸。已发现透明细胞肾细胞癌 (ccRCC) 的组织和尿液样本中 AFMID 显着下调。尽管ccRCC具有典型的Warburg样表型、线粒体功能障碍和脂肪沉积升高的特征，但AFMID是否在ccRCC的肿瘤发生和发展中发挥作用尚不清楚。在本研究中，AFMID 过表达对 ccRCC 细胞具有抑制作用，降低细胞增殖率。定量蛋白质组学表明，AFMID 过度表达改变了参与细胞生长和细胞代谢途径的细胞信号通路，包括脂质代谢和肌醇磷酸代谢。进一步的尿液蛋白质组分析表明，AFMID 过度表达的细胞功能障碍可以在尿液中反映出来。 ccRCC 细胞和尿液中预测的上调因子 DDX58、TREX1、TGFB1、SMARCA4 和 TNF 的活性显示出相反的变化趋势。使用独立队列初步发现并进一步验证了潜在的尿液生物标志物。 APOC3、UMOD 和 CILP 的蛋白质组在训练组中达到 0.862 的 AUC 值，在验证组中达到 0.883 的 AUC 值。本研究在强调与 AFMID 酶相关的途径变化的各个方面、发现用于潜在患者诊断和治疗靶向的潜在特异性生物标志物方面具有重要意义。

Aromatic caninurine formamase (AFMID) is an enzyme involved in the tryptophan pathway, metabolizing N-formylkynurenine to kynurenine. AFMID had been found significantly downregulated in clear cell renal cell carcinoma (ccRCC) in both tissue and urine samples. Although ccRCC is characterized by a typical Warburg-like phenotype, mitochondrial dysfunction, and elevated fat deposition, it is unknown whether AFMID plays a role in tumorigenesis and the development of ccRCC. In the present study, AFMID overexpression had inhibitory effects for ccRCC cells, decreasing the rate of cell proliferation. Quantitative proteomics showed that AFMID overexpression altered cellular signaling pathways involved in cell growth and cellular metabolism pathways, including lipid metabolism and inositol phosphate metabolism. Further urine proteomic analysis indicated that cellular function dysfunction with AFMID overexpression could be reflected in the urine. The activity of predicted upregulators DDX58, TREX1, TGFB1, SMARCA4, and TNF in ccRCC cells and urine showed opposing change trends. Potential urinary biomarkers were tentatively discovered and further validated using an independent cohort. The protein panel of APOC3, UMOD, and CILP achieved an AUC value of 0.862 for the training cohort and 0.883 for the validation cohort. The present study is of significance in terms of highlighting various aspects of pathway changes associated with AFMID enzymes, discovering potential specific biomarkers for potential patient diagnosis, and therapeutic targeting.