Department of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
Department of Radiology, Jiangmen Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, Guangdong, China.
BMC Cancer. 2024 Aug 28;24(1):1064. doi: 10.1186/s12885-024-12843-0.
Recent studies have increasingly linked Ephrin receptor B2 (EPHB2) to cancer progression. However, comprehensive investigations into the immunological roles and prognostic significance of EPHB2 across various cancers remain lacking.
We employed various databases and bioinformatics tools to investigate the impact of EPHB2 on prognosis, immune infiltration, genome instability, and response to immunotherapy. Validation of the correlation between EPHB2 expression and M2 macrophages included analyses using bulk and single-cell transcriptomic datasets, spatial transcriptomics, and multi-fluorescence staining. Moreover, we performed cMap web tool to screen for EPHB2-targeted compounds and assessed their potential through molecular docking and dynamics simulations. Additionally, in vitro validation using lung adenocarcinoma (LUAD) cell lines was conducted to confirm the bioinformatics predictions about EPHB2.
EPHB2 dysregulation was observed across multiple cancer types, where it demonstrated significant diagnostic and prognostic value. Gene Set Enrichment Analysis (GSEA) indicated that EPHB2 is involved in enhancing cellular proliferation, invasiveness of cancer cells, and modulation of the anti-cancer immune response. Furthermore, it is emerged as a pan-cancer marker for M2 macrophage infiltration, supported by integrated analyses of transcriptomics and multiple fluorescence staining. In LUAD cells, knockdown of EPHB2 expression led to a decrease in both cell proliferation and migratory activity.
EPHB2 expression may serve as a pivotal indicator of M2 macrophage infiltration, offering vital insights into tumor dynamics and progression across various cancers, including lung adenocarcinoma, highlighting its significant prognostic and therapeutic potential for further exploration.
最近的研究越来越多地将 Ephrin 受体 B2（EPHB2）与癌症进展联系起来。然而，全面研究 EPHB2 在各种癌症中的免疫作用和预后意义仍然缺乏。
我们使用各种数据库和生物信息学工具来研究 EPHB2 对预后、免疫浸润、基因组不稳定性和免疫治疗反应的影响。验证 EPHB2 表达与 M2 巨噬细胞之间的相关性包括使用批量和单细胞转录组数据集、空间转录组学和多荧光染色进行分析。此外，我们使用 cMap 网络工具筛选针对 EPHB2 的化合物，并通过分子对接和动力学模拟评估它们的潜力。此外，还使用肺腺癌（LUAD）细胞系进行了体外验证，以确认关于 EPHB2 的生物信息学预测。
EPHB2 在多种癌症类型中失调，表现出显著的诊断和预后价值。基因集富集分析（GSEA）表明 EPHB2 参与增强细胞增殖、癌细胞侵袭性和调节抗肿瘤免疫反应。此外，它作为 M2 巨噬细胞浸润的泛癌标志物得到了支持，这是通过转录组学和多种荧光染色的综合分析得出的。在 LUAD 细胞中，EPHB2 表达的敲低导致细胞增殖和迁移活性均降低。
EPHB2 表达可能是 M2 巨噬细胞浸润的关键指标，为各种癌症（包括肺腺癌）中的肿瘤动态和进展提供了重要的见解，突出了其在进一步探索中的重要预后和治疗潜力。
