单细胞与孟德尔随机化鉴定前列腺癌关键基因
DOI:
https://doi.org/10.70693/cjmsr.v1i2.1161Keywords:
前列腺癌；单细胞转录组测序；孟德尔随机化分析；表达数量性状位点；标记基因Abstract
摘 要：目的 利用单细胞转录组中差异表达基因结合全基因组关联研究(GWAS)数据的基因eQTL关联分析，以获得因果相关的前列腺癌（PCa）关键基因。方法 本研究利用GEO数据库中的GSE193337数据集，分析了8个前列腺组织样本的单细胞测序数据。通过R语言进行细胞聚类及注释并筛选各个细胞亚型标记基因。结合前列腺癌患者的GWAS和基因eQTL数据，进行孟德尔随机化（MR）分析，采用敏感性分析和异质性检验选择显著的基因结果。最后，构建蛋白互作网络，并进行GO和KEGG通路富集分析，筛选相关的功能通路。结果 本研究纳入8例前列腺样本（癌/正常各4例），注释为8种细胞类型（如T细胞、上皮细胞等）。MR分析鉴定上皮细胞差异基因IGFBP-3（OR=0.901，P=0.017）和TGM3（OR=1.042，P=0.009）与PCa因果关联，敏感性分析证实结果稳健。蛋白互作网络结合富集分析揭示关键基因参与前列腺癌、MAPK等通路，涉及生长调控及代谢过程。结论 本研究通过结合scRNA-seq和MR分析，确定了IGFBP-3和TGM3是PCa潜在的生物标志物。
项目：中央引导地方科技发展资金项目（YDZJSX20231A066）；山西省研究生实践创新项目（2024SJ170）
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