CLEC12B在肺腺癌中的表达及其与预后和免疫浸润的关系

Expression of CLEC12B in lung adenocarcinoma and its correlation with prognosis and immune infiltration

目的:C型凝集素受体(C-type lectin receptors,CLRs)家族参与发育、炎症调节、肿瘤、心血管疾病等许多病理和生理过程。C型凝集素结构域家族成员12B(C-type lectin domain family 12 member B,CLEC12B)能够抑制黑色素瘤增殖,但其与肺腺癌的关系尚不清楚。因此,本研究利用生物信息学方法探讨CLEC12B在肺腺癌中的表达水平及其与肿瘤分期、预后、免疫浸润的关系。方法:使用基因型-组织表达(genotype-tissue expression,GTEx)、癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库及免疫组织化学法探讨CLEC12B在肺腺癌中的表达及其与不同肿瘤分期的相关性,使用Kaplan-Meier Plotter在线分析网站、仙桃学术网页工具探讨CLEC12B与肺腺癌预后的相关性,并使用肿瘤免疫估算工具(tumor immune estimation resourse,TIMER)探究CLEC12B与免疫细胞浸润之间的相关性,再用基因表达谱互动分析(Gene Expression Profiling Interactive Analysis,GEPIA)数据库获取肺腺癌中表达相关的前100个与CLEC12B共表达的基因,进行基因本体(Gene Ontology,GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。结果:与正常组织相比,肺腺癌CLEC12B mRNA和蛋白表达水平下调。CLEC12B高表达与较早的肿瘤分期和较好的预后相关,并且B细胞、CD4+T细胞、CD8+T细胞、中性粒细胞等细胞浸润及免疫检查点基因的表达在CLEC12B高、低表达之间差异均有统计学意义(均P<0.05)。富集分析显示CLEC12B表达与中性粒细胞介导免疫、中性粒细胞脱颗粒等过程密切相关。结论:CLEC12B在肺腺癌中呈低表达,与中性粒细胞浸润、免疫检查点基因表达及中性粒细胞介导免疫、中性粒细胞脱颗粒等过程呈正相关,且CLEC12B低表达与较差的肺腺癌预后相关。

Objective:The C-type lectin receptor(CLR)family participates in various pathological and physiological processes such as development,inflammation regulation,tumors,and cardiovascular diseases.C-type lectin domain family 12 member B(CLEC12B)has been found to inhibit melanoma proliferation,but its relationship with lung adenocarcinoma(LUAD)remains unclear.Therefore,this study comprehensively explores the expression levels of CLEC12B in LUAD and its relationship with tumor staging,prognosis,and immune infiltration using bioinformatics methods.Methods:The Genotype-Tissue Expression(GTEx)database,The Cancer Genome Atlas(TCGA)database,and immunohistochemistry were used to investigate the expression of CLEC12B in LUAD and its correlation with different tumor stages.Kaplan-Meier Plotter and the Xiantao academic webpage tool were employed to investigate the correlation between CLEC12B and the prognosis of LUAD.The tumor immune estimation resourse(TIMER)algorithm was used to explore the correlation between CLEC12B and immune cell infiltration.Subsequently,the Gene Expression Profiling Interactive Analysis(GEPIA)database was utilized to identify the top 100 genes co-expressed with CLEC12B in LUAD,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.Results:Compared with the normal tissues,CLEC12B mRNA and protein expression levels were downregulated in LUAD.High expression of CLEC12B was associated with earlier tumor staging and better prognosis.The differences in the infiltration of B cells,CD4+T cells,CD8+T cells,neutrophils,and the expression of immune checkpoint genes between the high and low CLEC12B expression groups were statistically significant(all P<0.05).Enrichment analysis indicated that CLEC12B expression was closely related to processes such as neutrophil-mediated immunity and neutrophil degranulation.Conclusion:CLEC12B is downregulated in LUAD and positively correlated with neutrophil infiltration,immune checkpoint gene expression,and processes such as neutrophil-mediated immunity and neutrophil degranulation.Low expression of CLEC12B is associated with poor prognosis in LUAD.