基于孟德尔随机化和生物信息学方法鉴定胶质瘤发病关键基因及实验验证  

Identification and Experimental Verification of Key Genes in Glioma Based on Mendelian Randomization and Bioinformatics Methods

作　　者：赵茜 冯晓诗 苗野 Zhao Qian;Feng Xiaoshi;Miao Ye(The First Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000 China)

机构地区：[1]锦州医科大学附属第一医院,辽宁锦州121000

出　　处：《锦州医科大学学报》2024年第4期1-10,共10页Journal of Jinzhou Medical University

基　　金：辽宁省教育厅高等学校基本科研青年项目,项目编号:JYTQN2023430;锦州市指导性科技计划项目,项目编号:JZ2023B058。

摘　　要：目的鉴定和验证胶质瘤发生发展及预后的相关基因。方法利用孟德尔随机化方法筛选与胶质瘤发生风险相关的蛋白。基于TCGA数据库获取胶质瘤组织与癌旁组织的差异表达基因,整合风险蛋白和差异表达基因,并使用LASSO回归分析进一步筛选关键基因;使用ROC曲线、生存分析和免疫浸润分析方法评估关键基因与胶质瘤的关联效应;体外培养人胶质瘤U251细胞,构建干扰半乳糖凝集素3结合蛋白(lectin galactoside-binding soluble 3 binding protein,LGALS3BP)基因表达的siRNA序列,验证其对肿瘤细胞增殖、侵袭和迁移的影响。结果共发现34种血液蛋白与胶质瘤风险增加相关,30种蛋白与风险降低相关;与差异表达基因整合并进行LASSO回归分析后,7个关键基因包括IBSP、SEMA6B、PPIC、ISLR2、SCN2B、HAVCR2和LGALS3BP被确定。体外实验证实,干预LGALS3BP在胶质瘤细胞系U251中的表达可明显抑制肿瘤细胞增殖、迁移和侵袭能力。结论本研究基于孟德尔随机化、生物信息学方法鉴定胶质瘤发生发展及预后的相关新基因,并初步证实关键基因LGALS3BP在胶质瘤发生发展中的关键作用。Objective To identify and validate the genes related to the development and prognosis of glioma.Methods Proteins associated with glioma were screened by Mendelian randomization,the differentially expressed genes of glioma tissues and adjacent tissues were obtained based on TCGA database,risk proteins and differentially expressed genes were integrated,and key genes were further screened using LASSO regression analysis;ROC curve,survival analysis and immunoinfiltration analysis were used to evaluate the association effect of key genes with gliomas;human glioma U251 cells were cultured in vitro and soluble siRNA sequence interfering with the gene expression of lectin galactoside-binding 3 binding protein(LGALS3BP)was constructed to verify the effect on proliferation,invasion and migration of tumor cells.Results It was found that 34 genes were positively correlated with glioma and 30 genes were negatively correlated;after integration with differential expression genes and LASSO regression analysis,7 key genes including IBSP,SEMA6B,PPIC,ISLR2,SCN2B,HAVCR2 and LGALS3BP were identified.In vitro experiments confirmed that interfering with the expression of LGALS3BP in glioma cell line U251 could significantly inhibit the proliferation,migration and invasion of tumor cells.Conclusion In this study,new genes related to the development and prognosis of glioma were identified based on Mendelian randomization and bioinformatics methods,and the key gene LGALS3BP was preliminarily confirmed to play a key role in the development and progression of glioma.

关 键 词：胶质瘤 孟德尔随机化 差异表达分析 预后 LGALS3BP 

分 类 号：R739.4[医药卫生—肿瘤]