Multi-Omics Mendelian Randomization Integrating GWAS, eQTL, RNA-seq and Cell Line Experiment Reveal GLIPR1 and ARHGAP11A as Potential Targets of EGCG for Nasopharyngeal Carcinoma

Background: Epigallocatechin gallate (EGCG), a frequently studied catechin in green tea, has been shown to be involved in the antiproliferation and apoptosis of human Nasopharyngeal carcinoma (NPC) cells. Therefore, we aimed to find the drug targets that improve the prognosis of NPC. Methods: NPC cell line experiments, high-throughput sequencing, Mendelian Randomization (MR), expression quantitative trait loci (eQTL), and Summary-data-based MR (SMR) analyses were employed to identify potential EGCG targets in NPC using summary statistics from FinnGen cohorts (nCase = 152, nControl = 378,749). Validation was conducted via survival analysis and molecular docking. Genetic instruments derived from the eQTLGen database, combined with cell line experiments and RNA sequencing, enabled target confirmation at transcriptomic, proteomic, and molecular levels. Additional investigations included differential expression analysis, functional enrichment, immune cell correlation profiling, candidate drug prediction, and single-cell transcriptomic analysis. Results: MR analysis based on eQTL data identified 189 EGCG-associated genes significantly correlated with NPC risk in the FinnGen dataset. Among these, 16 targets satisfied SMR significance thresholds (p < 0.05) and passed the heterogeneity in dependent instruments (HEIDI) test (p > 0.05), indicating consistent associations at both gene expression and protein levels. Survival analysis of RNA-seq data revealed directional concordance only for GLIPR1 and ARHGAP11A—GLIPR1 exhibited a protective role, whereas ARHGAP11A correlated with increased NPC risk. Molecular docking confirmed strong binding affinities between EGCG and these targets, and functional assays demonstrated that EGCG upregulated GLIPR1 and suppressed ARHGAP11A expression in vitro. Transcriptomic differential analysis of the two genes elucidated their involvement in key biological processes and pathways. CIBERSORT-based immune infiltration analysis further indicated their relevance in modulating immune responses in NPC. Finally, single-cell transcriptome profiling delineated the gene-specific regulatory patterns of GLIPR1 and ARHGAP11A across diverse cellular subpopulations within the tumor microenvironment. Conclusion: This study has identified GLIPR1 and ARHGAP11A as potential therapeutic targets for EGCG, highlighting their significant roles in NPC.