Zhu Jun-Ming, Chen Shao-Hao, Xu Yi-Cheng, Gao Rui-Cheng, Cai Hai, Zheng Qing-Shui, Sun Xiong-Lin, Xue Xue-Yi, Wei Yong, Xu Ning
Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.
Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China.
Biochim Biophys Acta Mol Basis Dis. 2025 Mar;1871(3):167672. doi: 10.1016/j.bbadis.2025.167672. Epub 2025 Jan 23.
The aim of this work is to identify putative hub genes for the advancement of clear cell renal cell carcinoma (ccRCC) and determine the fundamental mechanisms.
We employed multiple bioinformatics techniques to screen hub genes. Key hub gene expression levels in ccRCC were assessed. A plethora of functional experiments were carried out to explore the biological role of hub gene. Based on genome-wide association studies, a Mendelian randomization research was conducted to ascertain the causative relationship between albumin (ALB) and ccRCC.
ALB was low expression in ccRCC tissues and cell lines. It was an independent predictor of progression-free survival following treatment and the overall survival of ccRCC patients. ALB overexpression exhibited the reverse effects of ALB knockdown, which increased cell proliferation, migration, and invasion while inhibiting cell death. Similarly, ALB overexpression inhibited the growth of ccRCC tumors in vivo. Consistent with functional enrichment analysis, ALB overexpression activates the endoplasmic reticulum stress (ERS) in vitro and vivo. The Mendelian randomization showed ALB was associated with the risk of ccRCC. Additionally, ALB was causally associated with γδT cells infiltrates in ccRCC.
ALB plays an important effect in ccRCC via activation of the ERS and regulating immune microenvironment.
本研究旨在鉴定与透明细胞肾细胞癌（ccRCC）进展相关的潜在枢纽基因，并确定其基本机制。
我们采用多种生物信息学技术筛选枢纽基因。评估了ccRCC中关键枢纽基因的表达水平。进行了大量功能实验以探究枢纽基因的生物学作用。基于全基因组关联研究，开展了孟德尔随机化研究以确定白蛋白（ALB）与ccRCC之间的因果关系。
ALB在ccRCC组织和细胞系中低表达。它是治疗后无进展生存期和ccRCC患者总生存期的独立预测指标。ALB过表达表现出与ALB敲低相反的作用，可增加细胞增殖、迁移和侵袭，同时抑制细胞死亡。同样，ALB过表达在体内抑制ccRCC肿瘤的生长。与功能富集分析一致，ALB过表达在体外和体内均可激活内质网应激（ERS）。孟德尔随机化显示ALB与ccRCC风险相关。此外，ALB与ccRCC中γδT细胞浸润存在因果关系。
ALB通过激活ERS和调节免疫微环境在ccRCC中发挥重要作用。
