Luo Zhouan, Wu Xiaoping, Xie Juanxia, Tang Hao, Chen Jingqi, Ye Dongcai, Dou Shangwen, Chen Songning
Department of Urology, Zhanjiang Central Hospital, Guangdong Medical University, No.236, Yuanzhu Road, Zhanjiang, Guangdong, 524045, China.
Department of Geriatrics, Zhanjiang Central Hospital, Guangdong Medical University, China.
Cancer Genet. 2025 Jan;290-291:6-15. doi: 10.1016/j.cancergen.2024.11.004. Epub 2024 Nov 9.
The F-box protein 8 Gene (FBXO8) has been shown to suppress invasion and metastasis in various cancer types. Recurrence and drug resistance pose significant challenges in renal cell carcinoma (RCC). Identifying novel biomarkers is crucial for addressing these issues.
Data on RNA sequencing and patient survival for KIRC was obtained from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. We confirmed FBXO8 gene expression and its impact on survival. Clinical characteristics were classified, and FBXO8 expression differences among various categories were observed. We conducted biofunctional predictions and analyzed the tumor microenvironment (TME), immune cell infiltration, and immune checkpoints in relation to FBXO8 expression. FBXO8 was overexpressed using a plasmid, and we assessed Kidney renal clear cell carcinoma (KIRC) cell proliferation, migration, and apoptosis through CCK8, wound healing tests, and western blot analysis.
Our findings revealed decreased FBXO8 expression in KIRC, with patients exhibiting low FBXO8 expression experiencing shorter survival times. The low expression group showed elevated TME immune and estimate scores. Biofunctional analyses indicated that FBXO8 expression was notably linked to drug metabolism cytochrome P450, nutrition disease, receptor-ligand activity, and neuroactive ligand-receptor interaction. Furthermore, we discovered significant correlations between FBXO8 expression and immune cell infiltration, as well as checkpoints such as CD274. Overexpression (OE) of FBXO8 led to a marked reduction in cell proliferation and migration, along with increased apoptosis, as evidenced by apoptosis-related protein expression.
This study demonstrates that FBXO8 serves as a biomarker for KIRC and plays a role in regulating cell proliferation, migration, and apoptosis.
F-box蛋白8基因(FBXO8)已被证明在多种癌症类型中可抑制侵袭和转移。复发和耐药性给肾细胞癌(RCC)带来了重大挑战。识别新型生物标志物对于解决这些问题至关重要。
从癌症基因组图谱(TCGA)、UALCAN和基因表达综合数据库(GEO)获取肾透明细胞癌(KIRC)的RNA测序和患者生存数据。我们确认了FBXO8基因表达及其对生存的影响。对临床特征进行分类,并观察不同类别之间FBXO8表达的差异。我们进行了生物功能预测,并分析了与FBXO8表达相关的肿瘤微环境(TME)、免疫细胞浸润和免疫检查点。使用质粒过表达FBXO8,并通过CCK8、伤口愈合试验和蛋白质印迹分析评估肾透明细胞癌(KIRC)细胞的增殖、迁移和凋亡。
我们的研究结果显示KIRC中FBXO8表达降低,FBXO8表达低的患者生存时间较短。低表达组的TME免疫和估计评分升高。生物功能分析表明,FBXO8表达与药物代谢细胞色素P450、营养疾病、受体-配体活性和神经活性配体-受体相互作用显著相关。此外,我们发现FBXO8表达与免疫细胞浸润以及CD274等检查点之间存在显著相关性。FBXO8的过表达(OE)导致细胞增殖和迁移显著减少,同时凋亡增加,凋亡相关蛋白表达证明了这一点。
本研究表明FBXO8作为KIRC的生物标志物,并在调节细胞增殖、迁移和凋亡中发挥作用。