肺腺癌骨转移癌痛患者外周血转录组学研究

Transcriptome profiling of peripheral blood cells in patients with metastatic bone painfrom lung adenocar-cinoma

目的研究肺腺癌骨转移癌痛(metastatic bone pain,MBP)患者外周血转录组学以阐释其发生发展中的关键基因和通路。方法选择我院呼吸内科肺腺癌骨转移住院患者11例,其中5例患者符合典型骨转移癌痛表现且疼痛视觉模拟评分≥4分(MBP组),6例视觉模拟评分为0分(C组)。收集两组患者外周血进行转录组测序,利用R语言筛选差异表达基因(differentially expressed genes,DEGs)并进行生物学功能富集分析。对DEGs进行蛋白质相互作用(protein-protein interaction,PPI)网络分析,获得最显著蛋白表达模块及关键基因,并结合TCGA临床数据对关键模块内基因进行生存分析。结果共获得差异基因共2332个,其中上调基因1647个,下调基因685个。GO和KEGG结果显示,DEGs主要富集在趋化因子转导通路和p53信号转导通路上。通过PPI网络分析及生存分析,筛选出4个关键节点基因(CXCL1、CXCL10、CXCR4和GNG7),其中GNG7与肺腺癌患者生存率密切相关。结论趋化因子/趋化因子受体CXCL1、CXCL10、CXCR4与GNG7可能作为MBP的重要预测因子和治疗靶点,为临床治疗提供依据。

Objective To analyze transcriptome profiling of peripheral blood cells of patients with metastatic bone pain(MBP)to screen key genes and pathways associated with the pathogenesis of the disease.Methods Peripheral blood samples from 11 lung adenocarcinoma patients with MBP were collected,including 5 patients with typical MBP clinical manifestations and visual analogue scale(VAS)≥4(Group MBP)and 6 patients without suffering any pain(Group C).Differentially expressed genes(DEGs)were screened by R language.GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathways analysis were performed on the DAVID database.The most significant module and key genes were analyzed by protein-protein interaction(PPI)network.Gene analysis results were combined with TCGA clinical follow-up data for survival analysis.Results A total of 2,332 DEGs were identified,consisting of 1,647 up-regulated genes and 685 down-regulated genes.The enriched processes and pathways of DEGs included Chemokine signaling pathway and p53 signaling pathway.The PPI network analysis and survival analysis identified 4 hub genes(CXCL1,CXCL10,CXCR54 and GNG7).Among them,GNG7 was closely related to the survival rate of lung adenocarcinoma patients.Conclusion GNG7 and certain chemokine/chemokine receptors such as CXCL1,CXCL10 and CXCR4 may be possible predictors and therapeutic targets for MBP,which could provide evidence for clinical treatment.