Integrated single-cell and Mendelian randomization analyses: dissecting underlying causes of varied efficacy in immune neoadjuvant therapy for esophageal carcinoma

整合单细胞和孟德尔随机化分析:剖析食管癌免疫新辅助治疗疗效差异的根本原因

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Abstract

BACKGROUND: Esophageal cancer has a low 5-year survival rate despite treatments. scRNA-seq and MR offer insights into neoadjuvant treatment efficacy for precision medicine. METHODS: Three post-neoadjuvant treatment datasets underwent QC for Seurat analysis. Marker genes identified cell subsets. MR analyzed eQTL data from GWAS cohorts for causal links. Single-cell and MR-derived genes intersected to reveal PLTP in CD4⁺T cells. RESULTS: Single-cell analysis of 16 samples found 40,198 genes and 120,102 cells. CD4⁺T cell numbers differed significantly between groups after therapy. Differentially expressed genes were immune-related. Pseudotime and cell-cell communication varied. PLTP, linked to esophageal cancer, co-expressed with genes involved in cell cycle processes. CONCLUSION: The study highlights CD4⁺T cells' predictive role in therapy efficacy via scRNA-seq and MR. PLTP emerges as a key gene, offering new precision medicine strategies for esophageal cancer.

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