摘要
目的 通过生物信息学方法筛选甲状腺癌(TC)新的生物标志物并探讨其对免疫浸润的影响.方法 从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)中获取5个TC相关数据集(GSE3467、GSE5364、GSE29265、GSE53157、TCGA-THCA)进行差异分析筛选出共同差异基因,然后用STRING构建它们的蛋白质互作(PPI)网络之后结合生存分析筛选出关键基因生长激素受体(GHR).使用单样本基因集富集(ssGSEA)和Spearman方法分析GHR表达与免疫细胞浸润和免疫调节基因表达之间的相关性.结果 对5个TC相关数据集进行差异分析并取交集获得66个差异基因,随后PPI网络分析鉴定到关键基因GHR在TC中的表达低于正常组织(P＜0.01),且高GHR组的生存概率显著低于低GHR组(P＜0.01).免疫浸润分析发现,GHR表达与辅助型T细胞17(Th17)、CD56dim自然杀伤(CD56dim NK)细胞和γδ T细胞等大多数免疫细胞的免疫浸润水平呈显著负相关(r=-0.41、-0.38、-0.35,P＜0.05),而与辅助型T细胞2(Th2)、嗜酸型粒细胞呈显著正相关(r=0.10、0.22,P＜0.05).GHR与大多数免疫调节基因的表达也呈显著负相关(r＜0,P＜0.05).结论 通过多个数据集鉴定到的关键基因GHR,其表达水平影响TC预后,通过影响免疫细胞浸润和免疫调节基因表达来影响TC的发生发展.
Abstract
Objective To screen new biomarkers of thyroid cancer(TC)and explore their effects on immune infiltration.Methods We selected 5 TC datasets[GSE3467,GSE5364,GSE29265,GSE53157,the cancer genome atlas(TCGA)-THCA]from gene expression omnibus(GEO)and TCGA and performed differential analysis to obtain differential genes.Then we constructed protein-protein interac-tion(PPI)network of differential genes based on STRING and selected the key gene growth hormone recep-tor(GHR)combined with survival analysis.Thereafter,we used the single-sample gene set enrichment a-nalysis(ssCSEA)and Spearman to analyze the correlation between GHR and immune cells infiltration and immunomodulatory genes.Results We performed differential analysis in 5 TC datasets,and a total of 66 differential genes were obtained after intersection.Subsequently,we screened the key gene GHR from the PPI network,whose expression in TC was lower than that in normal tissues(P＜0.01),and the survival probability of the high GHR group was significantly lower than that of the low GHR group(P＜0.01).We found that GHR expression was significantly negatively associated with the immune infiltration level of most immune cells including T helper 17(Th17),CD56dim natural killer(CD56dim NK)and γδ T cells(r=-0.41,-0.38,-0.35,P＜0.05),but showed a significantly positive correlation with T helper 2(Th2)cells and eosinophil(r=0.10,0.22,P＜0.05).GHR was also significantly negatively associated with the expression of most immunomodulatory genes(r＜0,P＜0.05).Conclusion GHR,a key gene i-dentified by multiple datasets,whose expression affects TC prognosis and affects the development of TC by affecting immune cell infiltration and immunomodulatory gene expression.
基金项目
河南省卫生健康中青年学科带头人项目(HNSWJW-2020004)
中原英才计划(育才系列)中原名医项目(ZYYCYU202012116)
NETL
NSTL
万方数据