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基于数据库筛选吸烟相关肺癌基因并探究其在肺癌中的意义OA北大核心CSTPCD

Screening smoking-related lung cancer genes based on databases and exploring their significance in lung cancer

中文摘要英文摘要

目的 筛选吸烟相关肺癌基因并探讨其在肺癌中的意义.方法 基于基因表达综合数据库(Gene Expression Omnibus,GEO)中吸烟相关数据集(GSE18385、GSE76324 和 GSE11906)和肺癌相关数据集(GSE27262、GSE31210 和GSE40791),分析吸烟和肺癌的差异表达基因(differentially expressed genes,DEGs)并用韦恩图取交集,基于癌症基因组图谱(TheCancer Genome Atlas,TCGA)验证DEGs在肺癌中的表达、预后风险及诊断价值并进一步筛选DEGs,通过人类蛋白质图谱(Human Protein Atlas,HPA)数据库再次验证DEGs在肺癌中的表达.基于TCGA数据库进行肺癌亚组预后风险分析,基因进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析、免疫浸润分析和免疫检查点相关性分析.结果 最终筛选到吸烟相关肺癌基因2个(SLC2A1、SLC7A5),它们在肺癌中表达均上调,单因素Cox和多因素Cox回归分析结果显示,SLC2A1和SLC7A5的高表达是肺癌的独立预后危险因素.在T分期、N分期、病理分期、吸烟者亚组中,SLC7A5和SLC2A1高表达的肺癌患者比低表达的肺癌患者总生存期显著缩短(P<0.05),提示SLC7A5和SLC2A1的高表达与肺癌的不良预后有关.基因富集分析显示与SLC7A5相关的基因主要富集在染色体,参与细胞周期、细胞衰老信号通路.免疫浸润分析结果提示SLC7A5和SLC2A1与多种免疫浸润细胞有关,免疫检查点相关性结果显示SLC7A5与CD276呈正相关(r=0.449,P<0.05),SLC2A1 与 CD276 呈正相关(r=0.543,P<0.05),SLC2A1 与 BTLA 和 BTN2A2 呈负相关(r<-0.350,P<0.05).结论 吸烟相关肺癌的差异基因SLC7A5和SLC2A1在肺癌中高表达并是肺癌的独立预后危险因素,具有较高的肺癌诊断价值.它们还与免疫浸润和免疫检查点有关,在调节肿瘤免疫中起重要作用,并具有较强的临床转化应用价值,可作为生物标志物为吸烟相关肺癌的临床预后评估和免疫治疗提供新思路.

Objective To screen smoking-related lung cancer genes and explore their significance in lung cancer.Methods Based on the smoking related datasets(GSE18385,GSE76324,and GSE11906)and lung cancer related datasets(GSE27262,GSE31210,and GSE40791)in the Gene Expression Omnibus(GEO)database,differentially expressed genes(DEGs)between smoking and lung cancer were analyzed and intersected using Wayne plots.The expression,prognostic risk,and diagnostic value of DEGs in lung cancer were validated using the The Cancer Genome Atlas(TCGA)database,and further screening of DEGs was conducted and re-verified in lung cancer through the Human Protein Atlas(HPA)database.Based on the TCGA database,prognostic risk analysis for lung cancer subgroups was performed,and genes were subjected to gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,immune infiltration analysis,and immune checkpoint correlation analysis.Results Two smoking-related lung cancer genes(SLC2A1 and SLC7A5)were ultimately screened,and their expression was upregulated in lung cancer.Univariate Cox and multivariate Cox regression analysis showed that the high expression of SLC2A1 and SLC7A5 was an independent prognostic risk factor for lung cancer.In the subgroups of T stage,N stage,pathological stage,and smokers,lung cancer patients with high expression of SLC7A5 and SLC2A1 had significantly shorter overall survival(P<0.05)compared to those with low expression,suggesting that high expression of SLC7A5 and SLC2A1 is associated with poor prognosis in lung cancer.Gene enrichment analysis shows that genes related to SLC7A5 are mainly enriched in chromosomes and participate in cell cycle and cell aging signaling pathways.The results of immune infiltration analysis suggest that SLC7A5 and SLC2A1 are associated with various immune infiltration cells.The correlation results of immune checkpoints show a positive correlation between SLC7A5 and CD276(r=0.449,P<0.05),a positive correlation between SLC2A1 and CD276(r=0.543,P<0.05),and a negative correlation between SLC2A1 and BTLA and BTN2A2(r<-0.35,P<0.05).Conclusions The differentially expressed genes SLC7A5 and SLC2A1 in smoking-related lung cancer are highly expressed and serve as independent prognostic risk factors for the disease,possessing significant diagnostic value for lung cancer.They are also related to immune infiltration and immune checkpoints,play an important role in regulating tumor immunity,and have strong clinical transformation application value.SLC7A5 and SLC2A1 can serve as a biomarker to provide new ideas for clinical prognosis evaluation and immunotherapy of smoking related lung cancer.

储云鹏;叶长青

南通大学公共卫生学院,江苏南通 226019

吸烟肺癌基因生物标志物生物信息学

SmokingLung cancerGenesBiomarkersBioinformatics

《中国医学前沿杂志(电子版)》 2024 (003)

40-49 / 10

南通市科技计划资助项目(MS12020076) Nantong Science and Technology Program Funding Project(MS12020076)

10.12037/YXQY.2024.03-08

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