背景:一些研究报道了Ephrin受体A2(EphA2)与多种癌症的恶性进展之间的重要关系。然而,缺乏对预后价值的全面泛癌分析,突变状态,甲基化景观,和EphA2的潜在免疫功能。
方法:使用癌症基因组图谱,基因型组织表达数据库和GEO数据,我们分析了正常组织和肿瘤组织中EphA2表达的差异以及EphA2对不同肿瘤预后的影响。此外,使用GSCALite,cBioPortal,TISDB,ULCLAN和TIMER2.0数据库或平台,我们全面分析了EphA2在33种不同肿瘤类型中的潜在致癌机制或表现,包括肿瘤突变状态,DNA甲基化状态与免疫细胞浸润。EphA2与免疫检查点的相关性,肿瘤突变负担,还计算了DNA微卫星不稳定性和DNA修复基因。最后,在细胞实验中验证了EphA2抑制剂对人神经胶质瘤和肺癌细胞增殖的影响。
结果:EphA2在不同肿瘤中差异表达,而过度表达的患者总体生存率较差。此外,基因突变,EphA2的基因拷贝数变异和DNA/RNA甲基化已在各种肿瘤中被鉴定。此外,EphA2与涉及巨噬细胞和CD8+T细胞的免疫浸润呈正相关。Further,在各种癌症中,EphA2mRNA表达与免疫检查点显着相关。特别是程序性死亡配体1。最后,EphA2抑制剂ALW-II-41-27显示出有效的抗肿瘤活性。
结论:我们对EphA2的首次泛癌症研究提供了对EphA2在不同肿瘤中的预后和免疫学作用的见解。提示EphA2可能是癌症不良预后和免疫浸润的潜在生物标志物。
BACKGROUND: Several studies have reported a significant relationship between Ephrin receptor A2 (EphA2) and malignant progression in numerous cancers. However, there is a lack of comprehensive pan-cancer analysis on the prognostic value, mutation status, methylation landscape, and potential immunological function of EphA2.
METHODS: Using The Cancer Genome Atlas, Genotype Tissue Expression Database and GEO data, we analysed the differences in EphA2 expression between normal and tumour tissues and the effects of EphA2 on the prognosis of different tumours. Furthermore, using GSCALite, cBioPortal, TISDB, ULCLAN and TIMER 2.0 databases or platforms, we comprehensively analysed the potential oncogenic mechanisms or manifestations of EphA2 in 33 different tumour types, including tumour mutation status, DNA methylation status and immune cell infiltration. The correlation of EphA2 with immune checkpoints, tumour mutational burden, DNA microsatellite instability and DNA repair genes was also calculated. Finally, the effects of EphA2 inhibitors on the proliferation of human glioma and lung cancer cells were verified in cellular experiments.
RESULTS: EphA2 is differentially expressed in different tumours, and patients with overexpression have poorer overall survival. In addition, gene mutations, gene copy number variation and DNA/RNA methylation of EphA2 have been identified in various tumours. Moreover, EphA2 is positively associated with immune infiltration involving macrophages and CD8+ T cells. Further, EphA2 mRNA expression is significantly associated with immune checkpoint in various cancers, especially programmed death-ligand 1. Finally, the EphA2 inhibitor ALW-II-41-27 shows potent anti-tumour activity.
CONCLUSIONS: Our first pan-cancer study of EphA2 provides insight into the prognostic and immunological roles of EphA2 in different tumours, suggesting that EphA2 might be a potential biomarker for poor prognosis and immune infiltration in cancer.