基于生物生信学探究骨膜蛋白在非小细胞肺癌中表达及功能
Study on the expression and function of periostin in non-small cell lung cancer based on bioinformatics
王行楷 1范玉萧 1许文昊 1袁琦1
作者信息
- 1. 牡丹江医科大学,黑龙江 牡丹江 157011
- 折叠
摘要
目的 研究骨膜蛋白(Periostin,POSTN)在非小细胞肺癌(Non-small cell lung cancer,NSCLC)中表达及其调控机制.方法 使用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库和基因表达综合数据库(Gene Expression Omnibus,GEO)数据库分析NSCLC腺癌患者中POSTN的表达;使用cBioQPortal数据库进行基因突变分析;基于 ESTIMATE算法和CIBERSORT算法分析免疫细胞浸润;基因集富集分析(Gene set enrichment analysis,GSEA)和细胞实验探究POSTN对糖酵解信号通路的调控作用.结果 POSTN在NSCLC腺癌肿瘤组织中表达升高(TCGA:P<0.000 1,GSE159857:P=0.001 4);与POSTN低表达患者相比,POSTN高表达患者基因突变率(90.21%vs 83.64%)和促肿瘤免疫细胞显著升高[M0 巨噬细胞(P=0.000 74)和中性粒细胞(P=0.002 3)];功能富集分析表明POSTN激活糖酵解信号通路(P<0.001,FDR<0.001,NES=1.671);细胞实验证实POSTN重组蛋白促进肺癌细胞的葡萄糖消耗(P=0.001)、乳酸生成(P=0.000 2)和ATP产生(P=0.004 2).结论 POSTN通过调节免疫反应和有氧糖酵解促进了NSCLC腺癌进展,靶向POSTN将为NSCLC腺癌患者的靶向治疗提供策略.
Abstract
Objective To investigate the expression and regulatory mechanism of periostin(POSTN)in non-small cell lung cancer(NSCLC).Methods The expression of POSTN in NSCLC patients was analyzed using The Cancer Genome Atlas(TCGA)da-tabase and Gene Expression Omnibus(GEO)database.Gene mutation analysis was performed using the cBioQPortal database.Infiltra-tion of immune cells was analyzed based on ESTIMATE algorithm and CIBERSORT algorithm.The regulatory effect of POSTN on glycol-ysis signaling pathway was explored using Gene set enrichment analysis(GSEA)and cellular experiments.Results The expression of POSTN was increased in NSCLC tissues(TCGA:P<0.000 1,GSE159857:P=0.001 4).Compared to patients with low POSTN expres-sion,those with high POSTN expression exhibited a higher gene mutation rate(90.21%vs 83.64%)and increased tumor-promoting immune cells,including M0 macrophages(P=0.000 74)and neutrophils(P=0.002 3).Functional enrichment analysis revealed that POSTN activated glycolysis signaling pathway(P<0.001,FDR<0.001,NES=1.671).Cellular experiments confirmed that POSTN re-combinant protein enhances glucose consumption(P=0.001),lactate production(P=0.000 2)and ATP production(P=0.004 2)in lung cancer cells.Conclusion POSTN promotes the progression of NSCLC by modulating immune responses and aerobic glycolysis.Tar-geting POSTN may provide strategies for targeted therapy of NSCLC patients.
关键词
骨膜蛋白/非小细胞肺癌/糖酵解/基因突变/肿瘤微环境Key words
Periostin/Non-small cell lung cancer/Glycolysis/Gene mutation/Tumor microenvironment引用本文复制引用
出版年
2025
NETL
NSTL
万方数据