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睾丸生殖细胞肿瘤免疫微环境中新生物标志物的鉴定

Identification of new biomarkers in immune microenvironment of testicular germ cell tumour.

作者信息

Song Yuxuan, Qi Xiangjie, Kang Jiaqi, Wang Xiao, Ou Ningjing, Zhu Jun, Wang Shangren, Liu Xiaoqiang

机构信息

Department of Urology, Tianjin Medical University General Hospital, Tianjin, China.

Department of Urology, Linzi District People's Hospital, Zibo, China.

出版信息

Andrologia. 2021 Apr;53(3):e13986. doi: 10.1111/and.13986. Epub 2021 Feb 5.

Abstract

To seek novel prognostic biomarkers for testicular germ cell tumour (TGCT) and investigate the tumour immune microenvironment, we identified critical differentially expressed genes (DEGs) by overlapping GSE1818 dataset from Gene Expression Omnibus (GEO). Protein-protein interaction (PPI) network was used to investigate key modules and hub genes. Functional enrichment analysis was performed to investigate the underlying molecular functions of the DEGs in TGCT development and progression. The following survival analysis based on The Cancer Genome Atlas (TCGA) TGCT dataset indicated that AKAP4, SPA17 and TNP1 are correlated with TGCT prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction verified the down-regulation of the 3 hub genes in TGCT. Gene set enrichment analysis was conducted to further explore the role of the 3 hub genes in TGCT respectively. In addition, TGCT samples had high infiltration of CD8+ T cells, M0 and M1 macrophage cells, and resting myeloid dendritic cells in immune microenvironment. We also constructed the microRNA-gene regulatory networks to identify the key upstream microRNAs in TGCT. In conclusion, our findings indicated that AKAP4, SPA17 and TNP1 are promising biomarkers of TGCT. AKAP4 and TNP1 might regulate immune cells infiltration in immune microenvironment.

摘要

为寻找睾丸生殖细胞肿瘤(TGCT)的新型预后生物标志物并研究肿瘤免疫微环境,我们通过重叠来自基因表达综合数据库(GEO)的GSE1818数据集,鉴定出关键的差异表达基因(DEG)。利用蛋白质-蛋白质相互作用(PPI)网络研究关键模块和枢纽基因。进行功能富集分析以研究DEG在TGCT发生发展中的潜在分子功能。基于癌症基因组图谱(TCGA)的TGCT数据集进行的生存分析表明,AKAP4、SPA17和TNP1与TGCT预后相关。免疫组织化学和定量实时聚合酶链反应验证了TGCT中这3个枢纽基因的下调。分别进行基因集富集分析以进一步探索这3个枢纽基因在TGCT中的作用。此外,TGCT样本在免疫微环境中CD8 + T细胞、M0和M1巨噬细胞以及静息髓样树突状细胞的浸润较高。我们还构建了微小RNA-基因调控网络以鉴定TGCT中的关键上游微小RNA。总之,我们的研究结果表明,AKAP4、SPA17和TNP1是有前景的TGCT生物标志物。AKAP4和TNP1可能调节免疫微环境中免疫细胞的浸润。

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