基于GEO数据库鉴定ADIPOQ为脂肪肉瘤预后良好的生物标志物

Identification of ADIPOQ as a favorable prognostic biomarker for liposarcoma based on GEO database

目的探寻脂肪肉瘤的预后生物标志物,以作为其潜在的治疗靶点。方法从基因表达综合数据库(Gene Expression Omnibus,GEO)中下载GSE21122、GSE159659及GSE30929数据集,采用R语言limma包鉴定脂肪肉瘤与正常脂肪组织间的显著差异基因,利用ggvenn包获得共同差异基因。利用survival和survminer包进行Cox回归分析和Kaplan-Meier生存分析。采用corr.text函数分析ADIPOQ与多种免疫检查点分子的相关性。利用clusterProfiler包对高低表达ADIPOQ脂肪肉瘤之间的差异表达基因进行功能富集分析。结果在GSE21122和GSE159659数据集中,分别鉴定出155个和39个显著差异基因。Venn图显示存在25个共同差异基因。多因素Cox回归分析结果显示,ADIPOQ可作为脂肪肉瘤预后良好的独立因素[HR=0.68,95%CI(0.49,0.94),P=0.022]。与正常脂肪组织相比,ADIPOQ在脂肪肉瘤组织中显著低表达(P<0.001)。Kaplan-Meier生存分析结果显示,高表达ADIPOQ脂肪肉瘤患者的无远处复发生存期(distant recurrence free survival,DRFS)显著高于低表达组(P<0.001)。Spearman相关性分析结果显示,ADIPOQ与ICOS、TNFSF9、LAG3、CTLA4、CD47、CD200、CD86、PDCD1LG2等免疫检查点分子量呈负相关关系(P<0.05)。基因本体(GeneOntology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genesand Genomes,KEGG)分析结果显示,高低表达ADIPOQ脂肪肉瘤之间的上调基因在营养物质代谢及相关通路中富集,下调基因在细胞分裂、细胞周期等生物学功能中富集。结论ADIPOQ可作为脂肪肉瘤患者预后良好的生物标志物,其可能具有抑制多种免疫检查点表达的作用,从而改善脂肪肉瘤患者的预后。

Objective To explore the prognostic biomarkers for liposarcoma as potential therapeutic targets.Methods GSE21122,GSE159659,and GSE30929 datasets were downloaded from Gene Expression Omnibus(GEO)database.The significantly differentially expressed genes between liposarcoma and normal adipose tissues were identified using the limma package of R language.The common differentially expressed genes were obtained using the ggvenn package.The survival and survminer packages were performed for Cox regression analysis and Kaplan-Meier survival analysis.The correlation between ADIPOQ and multiple immune checkpoint molecules was analyzed using the corr.text function.Functional enrichment analysis of differentially expressed genes between liposarcomas with high and low ADIPOQ was performed by clusterProfiler package.Results In GSE21122 and GSE159659 datasets,155 and 39 significantly differentially expressed genes were identified,respectively.The Venn plot displayed the 25 common differentially expressed genes.Multivariate Cox regression analysis showed that ADIPOQ could serve as an independent factor for the favorable prognosis of liposarcoma[HR=0.68,95%CI(0.49,0.94),P=0.022].Compared with normal adipose tissues,ADIPOQ was significantly downregulated in liposarcoma tissues(P<0.001).Kaplan-Meier survival analysis showed that liposarcoma patients with high level of ADIPOQ had significantly longer distant recurrence free survival(DRFS)than those with low ADIPOQ(P<0.001).Spearman correlation analysis showed that ADIPOQ was negatively correlated with immune checkpoint molecules such as ICOS,TNFSF9,LAG3,CTLA4,CD47,CD200,CD86,and PDCD1LG2(P<0.05).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses revealed that the upregulated genes between liposarcomas with high and low ADIPOQ were abundant in nutrient metabolism and metabolism-related pathways,while downregulated genes were involved in biological function of cell division and cell cycle.Conclusion ADIPOQ could serve as a favorable prognostic biomarker for liposarcoma,and it may have the effect of inhibiting the expression of multiple immune checkpoints,thereby improving the prognosis of liposarcoma patients.