Comprehensive analysis of EphA2 in pan-cancer: A prognostic biomarker associated with cancer immunity

IF 2.9 4区医学 Q2 Medicine Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-06-17 DOI:10.1111/1440-1681.13902

Yuchun Li, Hanxiao Fei, Zhiwen Xiao, Xiuxia Lu, Hua Zhang, Mengmeng Liu

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Abstract

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.

Method

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.

Conclusion

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.

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全面分析泛癌症中的 EphA2：与癌症免疫相关的预后生物标志物

背景：一些研究报告称，Ephrin受体A2（EphA2）与多种癌症的恶性进展之间存在重要关系。然而，目前还缺乏对 EphA2 的预后价值、突变状态、甲基化情况以及潜在免疫功能的全面泛癌症分析：方法：我们利用癌症基因组图谱、基因型组织表达数据库和 GEO 数据，分析了 EphA2 在正常组织和肿瘤组织中的表达差异，以及 EphA2 对不同肿瘤预后的影响。此外，我们还利用 GSCALite、cBioPortal、TISDB、ULCLAN 和 TIMER 2.0 数据库或平台，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 甲基化状态和免疫细胞浸润。研究还计算了EphA2与免疫检查点、肿瘤突变负荷、DNA微卫星不稳定性和DNA修复基因的相关性。最后，在细胞实验中验证了 EphA2 抑制剂对人类胶质瘤和肺癌细胞增殖的影响：结果：EphA2在不同肿瘤中有不同的表达，过度表达的患者总生存率较低。此外，在各种肿瘤中还发现了 EphA2 的基因突变、基因拷贝数变异和 DNA/RNA 甲基化。此外，EphA2 与涉及巨噬细胞和 CD8+ T 细胞的免疫浸润呈正相关。最后，EphA2抑制剂ALW-II-41-27显示出了强大的抗肿瘤活性：我们首次对EphA2进行的泛癌症研究深入揭示了EphA2在不同肿瘤中的预后和免疫学作用，表明EphA2可能是癌症不良预后和免疫浸润的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical and Experimental Pharmacology and Physiology 医学-生理学

CiteScore

6.20

自引率

0.00%

发文量

128

审稿时长

6 months

期刊介绍： Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.