Jiang Kun, Xu Li-Zhe, Ning Jin-Zhuo, Cheng Fan
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
Cancer Cell Int. 2023 Sep 27;23(1):217. doi: 10.1186/s12935-023-03073-8.
Herein, we aimed at exploring the FAP expression in clear cell renal cell carcinoma (ccRCC) along with its clinical implication.
Using computational tools analysis of different freely accessible gene databases, the expression pattern, clinical importance, co-expressed genes, and signaling pathways of FAP in ccRCC were thoroughly investigated. FAP expression was examined in clinical ccRCC specimens through qRT-PCR, western blotting and immunohistochemistry. Furthermore, in vitro and in vivo experiments were carried out using flow cytometry, CCK-8, wound-healing and Transwell assays, as well as xenograft tumor model, respectively.
FAP levels were found to be significantly elevated in ccRCC based on bioinformatic data from public databases. Patients who exhibited higher expression levels of FAP had poorer prognoses, according to Kaplan-Meier analysis of survival data. In addition, diagnostic and prognostic value of FAP in ccRCC was figured out by ROC curve and prognostic nomogram model. In vitro study revealed that the over-expression FAP accelerated cell proliferation, migration as well as invasion, and suppressed cell apoptosis, but silencing of FAP had the opposite effect. FAP suppression reduced the PI3K/AKT/mTOR pathway's stimulation, whereas FAP up-regulation increased the stimulation of the pathway. Blocking the PI3K/AKT/mTOR signaling pathway with the dual PI3K/mTOR inhibitor BEZ235 repressesed cancer-promoting effect of FAP. Additionally, we found that the downregulation of FAP was effective at slowing tumor progression in vivo.
It is possible that FAP could be a reliable biomarker for the diagnosis and prognosis of ccRCC because of its role in the ccRCC progression via triggering the PI3K/AKT/mTOR signaling pathway.
在此，我们旨在探究透明细胞肾细胞癌（ccRCC）中FAP的表达及其临床意义。
利用计算工具对不同可免费获取的基因数据库进行分析，深入研究ccRCC中FAP的表达模式、临床重要性、共表达基因和信号通路。通过qRT-PCR、蛋白质免疫印迹法和免疫组织化学法检测临床ccRCC标本中的FAP表达。此外，分别使用流式细胞术、CCK-8、伤口愈合和Transwell实验以及异种移植肿瘤模型进行体外和体内实验。
基于来自公共数据库的生物信息学数据，发现ccRCC中FAP水平显著升高。根据生存数据的Kaplan-Meier分析，FAP表达水平较高的患者预后较差。此外，通过ROC曲线和预后列线图模型确定了FAP在ccRCC中的诊断和预后价值。体外研究表明，FAP的过表达加速了细胞增殖、迁移和侵袭，并抑制了细胞凋亡，但FAP沉默则产生相反的效果。FAP抑制降低了PI3K/AKT/mTOR通路的激活，而FAP上调则增加了该通路的激活。用双PI3K/mTOR抑制剂BEZ235阻断PI3K/AKT/mTOR信号通路可抑制FAP的促癌作用。此外，我们发现FAP的下调在体内有效减缓了肿瘤进展。
FAP可能是ccRCC诊断和预后的可靠生物标志物，因为它通过触发PI3K/AKT/mTOR信号通路在ccRCC进展中发挥作用。
