Integrating Single-cell RNA Sequencing and Mendelian Randomization Reveals the Pathogenic Mechanism of Eomes in Renal Cell Carcinoma
10.13241/j.cnki.pmb.2025.15.003
- VernacularTitle:基于单细胞RNA-Seq与孟德尔随机化联合分析Eomes在肾细胞癌中的作用机制
- Author:
Xin-cen WANG
1
;
Hai-xia HUANG
;
Xin-hao WANG
;
Zhi-fei CHE
;
Pei-yu LIANG
Author Information
1. 海南医科大学第一附属医院泌尿外科 海南海口 570100
- Publication Type:Journal Article
- Keywords:
Single-cell RNA sequencing;
Mendelian randomization;
Renal cell carcinoma;
Eomes
- From:
Progress in Modern Biomedicine
2025;25(15):2421-2430
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study employs a combination of single-cell sequencing and Mendelian randomization to explore the genetic associations and molecular mechanisms of Eomes in RCC.Methods:In this study,single-cell transcriptomic data from RCC tissues and adjacent normal tissues were extracted from the GEO database.The data were analyzed using R language and various packages such as Seurat,limma,and CellChat for cell cluster annotation,intercellular communication analysis,and differential expression analysis.Additionally,eQTL data related to differentially expressed genes were retrieved from the GWAS database as exposure variables,with RCC used as the outcome variable in Mendelian randomization analysis to identify the role of Eomes in RCC.Finally,GO functional enrichment and KEGG pathway analyses were conducted to explore the potential molecular mechanisms of Eomes.Results:Single-cell RNA sequencing revealed that B cells play a significant role in the heterogeneity of RCC.Mendelian randomization analysis indicated that Eomes is an important risk factor for RCC(P＜0.05).Furthermore,seven highly correlated specific SNPs were identified,including rs 17021298,rs2247056,rs2617170,rs3806624,rs55908509,rs6590334,and rs9420589.GO and KEGG enrichment analyses suggest that Eomes may be involved in early cell fate determination in renal cell carcinoma and participate in the regulation of Th1 and Th2 cell differentiation,HPV infection,and the Notch signaling pathway.Conclusions:This study is the first to combine single-cell sequencing and Mendelian randomization analysis in RCC,confirming a strong positive causal relationship between Eomes and RCC(OR＞1).Our findings offer new insights into the pathogenesis of RCC,suggesting that Eomes could serve as a novel target for early diagnosis and personalized treatment of RCC.
