Zhao Yiqiao, Yang Liang, Bai Xiaojie, Du Lu, Lai Huan, Liu Yiyang, Chen Ping, DiSanto Michael E, Zhang Xinhua
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
Sci Rep. 2025 Jan 25;15(1):3192. doi: 10.1038/s41598-025-86644-1.
Clear cell renal cell carcinoma is a prevalent urological malignancy, imposing substantial burdens on both patients and society. In our study, we used bioinformatics methods to select four putative target genes associated with EMT and prognosis and developed a nomogram model which could accurately predicting 5-year patient survival rates. We further analyzed proteome and single-cell data and selected PLCG2 and TMEM38A for the following experiments. Overexpression models of PLCG2 and TMEM38A were generated in Caki-1 and 786-O cell lines using plasmids. The in vitro experiments demonstrated that both of them exerted pro-apoptotic effects on Caki-1 and 786-O cells, inducing G2/M phase arrest, inhibiting proliferation, and suppressing EMT. In summary, we identified potential tumor suppressor factors and stratified ccRCC patients into high-risk and low-risk groups based on these factors. Furthermore, we elucidated the impact of PLCG2 and TMEM38A in Caki-1 and 786-O cell lines, offering novel avenues for therapeutic target exploration.
透明细胞肾细胞癌是一种常见的泌尿系统恶性肿瘤,给患者和社会都带来了沉重负担。在我们的研究中,我们使用生物信息学方法筛选出四个与上皮-间质转化(EMT)和预后相关的假定靶基因,并开发了一种列线图模型,该模型能够准确预测患者的5年生存率。我们进一步分析了蛋白质组和单细胞数据,并选择磷脂酶Cγ2(PLCG2)和跨膜蛋白38A(TMEM38A)进行后续实验。使用质粒在Caki-1和786-O细胞系中构建了PLCG2和TMEM38A的过表达模型。体外实验表明,它们对Caki-1和786-O细胞均具有促凋亡作用,诱导G2/M期阻滞,抑制增殖,并抑制EMT。总之,我们鉴定出了潜在的肿瘤抑制因子,并基于这些因子将透明细胞肾细胞癌患者分为高风险和低风险组。此外,我们阐明了PLCG2和TMEM38A在Caki-1和786-O细胞系中的作用,为治疗靶点探索提供了新途径。