基于生物信息学分析甲状腺癌中生长激素受体与免疫浸润水平的相关性研究  

Correlation between growth hormone receptor and the level of immune infiltration in thyroid cancer based on bioinformatics analysis

作　　者：贾勐[1] 秦晔 梁佳雯 李仟千 王鑫涛 王浩[1] 王洁 王俭伟 卢秀波[1] Jia Meng;Qin Ye;Liang Jiawen;Li Qianqian;Wang Xintao;Wang Hao;Wang Jie;Wang Jianwei;Lu Xiubo(Department of Thyroid,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Computer and Artificial Intelligence School,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州大学第一附属医院甲状腺外科,郑州450052 [2]郑州大学计算机与人工智能学院,郑州450001

出　　处：《中华实验外科杂志》2024年第5期956-958,共3页Chinese Journal of Experimental Surgery

基　　金：河南省卫生健康中青年学科带头人(HNSWJW-2020004);中原英才计划(育才系列)中原名医(ZYYCYU202012116)。

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γδT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。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 interaction(PPI)network of differential genes based on STRING and selected the key gene growth hormone receptor(GHR)combined with survival analysis.Thereafter,we used the single-sample gene set enrichment analysis(ssGSEA)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)andγδT 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 identified by multiple datasets,whose expression affects TC prognosis and affects the development of TC by affecting immune cell infiltration and immunomodulatory gene expression.

关 键 词：甲状腺癌 生长激素受体 免疫细胞 浸润 

分 类 号：R736.1[医药卫生—肿瘤]