YTHDF1是一种用于预后和免疫治疗的潜在泛癌生物标志物。
YTHDF1 Is a Potential Pan-Cancer Biomarker for Prognosis and Immunotherapy.
作者信息
Hu Jian, Qiu Dongxu, Yu Anze, Hu Jiao, Deng Hao, Li Huihuang, Yi Zhenglin, Chen Jinbo, Zu Xiongbing
机构信息
Department of Urology, Xiangya Hospital, Central South University, Changsha, China.
出版信息
Front Oncol. 2021 May 6;11:607224. doi: 10.3389/fonc.2021.607224. eCollection 2021.
BACKGROUND
YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) has been indicated proven to participate in the cross-presentation of tumor antigens in dendritic cells and the cross-priming of CD8+ T cells. However, the role of YTHDF1 in prognosis and immunology in human cancers remains largely unknown.
METHODS
All original data were downloaded from TCGA and GEO databases and integrated R 3.2.2. YTHDF1 expression was explored with the Oncomine, TIMER, GEPIA, and BioGPS databases. The effect of YTHDF1 on prognosis was analyzed GEPIA, Kaplan-Meier plotter, and the PrognoScan database. The TISIDB database was used to determine YTHDF1 expression in different immune and molecular subtypes of human cancers. The correlations between YTHDF1 expression and immune checkpoints (ICP), tumor mutational burden (TMB), microsatellite instability (MSI), and neoantigens in human cancers were analyzed the SangerBox database. The relationships between YTHDF1 expression and tumor-infiltrated immune cells were analyzed the TIMER and GEPIA databases. The relationships between YTHDF1 and marker genes of tumor-infiltrated immune cells in urogenital cancers were analyzed for confirmation. The genomic alterations of YTHDF1 were investigated with the c-BioPortal database. The differential expression of YTHDF1 in urogenital cancers with different clinical characteristics was analyzed with the UALCAN database. YTHDF1 coexpression networks were studied by the LinkedOmics database.
RESULTS
In general, YTHDF1 expression was higher in tumors than in paired normal tissue in human cancers. YTHDF1 expression had strong relationships with prognosis, ICP, TMB, MSI, and neoantigens. YTHDF1 plays an essential role in the tumor microenvironment (TME) and participates in immune regulation. Furthermore, significant strong correlations between YTHDF1 expression and tumor immune-infiltrated cells (TILs) existed in human cancers, and marker genes of TILs were significantly related to YTHDF expression in urogenital cancers. TYHDF1 coexpression networks mostly participated in the regulation of immune response and antigen processing and presentation.
CONCLUSION
YTHDF1 may serve as a potential prognostic and immunological pan-cancer biomarker. Moreover, YTHDF1 could be a novel target for tumor immunotherapy.
背景
YTH N6-甲基腺苷RNA结合蛋白1（YTHDF1）已被证实参与树突状细胞中肿瘤抗原的交叉呈递以及CD8+T细胞的交叉启动。然而，YTHDF1在人类癌症的预后和免疫学中的作用仍 largely未知。
方法
所有原始数据均从TCGA和GEO数据库下载，并整合到R 3.2.2中。使用Oncomine、TIMER、GEPIA和BioGPS数据库探索YTHDF1的表达。使用GEPIA、Kaplan-Meier plotter和PrognoScan数据库分析YTHDF1对预后的影响。使用TISIDB数据库确定YTHDF1在人类癌症不同免疫和分子亚型中的表达。使用SangerBox数据库分析YTHDF1表达与人类癌症中的免疫检查点（ICP）、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和新抗原之间的相关性。使用TIMER和GEPIA数据库分析YTHDF1表达与肿瘤浸润免疫细胞之间的关系。分析YTHDF1与泌尿生殖系统癌症中肿瘤浸润免疫细胞的标记基因之间的关系以进行确认。使用c-BioPortal数据库研究YTHDF1的基因组改变。使用UALCAN数据库分析YTHDF1在具有不同临床特征的泌尿生殖系统癌症中的差异表达。通过LinkedOmics数据库研究YTHDF1共表达网络。
结果
总体而言，在人类癌症中，肿瘤中的YTHDF1表达高于配对的正常组织。YTHDF1表达与预后、ICP、TMB、MSI和新抗原密切相关。YTHDF1在肿瘤微环境（TME）中起重要作用并参与免疫调节。此外，在人类癌症中，YTHDF1表达与肿瘤免疫浸润细胞（TILs）之间存在显著的强相关性，并且在泌尿生殖系统癌症中，TILs的标记基因与YTHDF表达显著相关。TYHDF1共表达网络主要参与免疫反应以及抗原加工和呈递的调节。
结论
YTHDF1可能作为一种潜在的预后和免疫泛癌生物标志物。此外，YTHDF1可能是肿瘤免疫治疗的新靶点。
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