Guo Songyue, Yu Yanan, Bu Yulan, Ren Jiao, Zhang Lu, Ma Xiaolin, Li Jiaqiu, Li Ao, Liu Xinling
Department of Oncology, School of Clinical Medicine, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang, 261053, Shandong, China.
Clinical Research Center, Affiliated Hospital of Shandong Second Medical University, Shandong Second Medical University, Weifang, 261053, Shandong, China.
Clin Transl Oncol. 2024 Dec 18. doi: 10.1007/s12094-024-03818-5.
ANGPT2 plays important roles in cancer development. However, there is still no systematic analysis of ANGPT2 in pan-cancer.
In this paper, we conducted a pan-cancer analysis to investigate the characteristics of ANGPT2. Furthermore, we investigated the impact of genetic and epigenetic factors on ANGPT2 expression by bioinformatics and assays.
By several TCGA and GEO databases, we identified elevated expression of ANGPT2 in various tumor types. Besides, high expression of ANGPT2 induced poor prognosis of patients in multiple tumors. Through enrichment analysis, we found that ANGPT2 participated in various biological processes, including angiogenesis and immunity. Various immune analyses indicated that high expression of ANGPT2 might suggest a propensity towards a hot tumor microenvironment, but its impact on immunotherapy was negative. Bioinformatics analysis and experiments confirmed that genetic and epigenetic factors explained part of the mechanism behind ANGPT2 abnormal expression. Finally, we screened candidate drugs targeting the ANGPT2 protein by molecular docking and molecular dynamics simulation.
ANGPT2 has diagnostic and prognostic values in multiple tumor types. Though with a hot tumor microenvironment, ANGPT2 high expression patients are not suitable for immunotherapy because of its proangiogenic function, contributing to selecting the exact patients for immunotherapy. Both genetic and epigenetic factors influenced ANGPT2 expression, with the influence of super-enhancer being more pronounced. This paper for the first time did the systematic analysis of ANGPT2 and showed its characteristic in pan-cancer. We summarized the biomarker role of ANGPT2 on tumor diagnosis and prognosis, as well as its target role on tumor immunotherapy.
血管生成素2（ANGPT2）在癌症发展中起重要作用。然而，目前尚无关于ANGPT2在泛癌中的系统分析。
在本文中，我们进行了泛癌分析以研究ANGPT2的特征。此外，我们通过生物信息学和实验研究了遗传和表观遗传因素对ANGPT2表达的影响。
通过多个癌症基因组图谱（TCGA）和基因表达综合数据库（GEO），我们发现ANGPT2在多种肿瘤类型中表达升高。此外，ANGPT2高表达导致多种肿瘤患者预后不良。通过富集分析，我们发现ANGPT2参与了包括血管生成和免疫在内的各种生物学过程。各种免疫分析表明，ANGPT2高表达可能提示肿瘤微环境呈“热”状态，但其对免疫治疗的影响是负面的。生物信息学分析和实验证实，遗传和表观遗传因素解释了ANGPT2异常表达背后的部分机制。最后，我们通过分子对接和分子动力学模拟筛选了靶向ANGPT2蛋白的候选药物。
ANGPT2在多种肿瘤类型中具有诊断和预后价值。尽管肿瘤微环境呈“热”状态，但由于ANGPT2的促血管生成功能，ANGPT2高表达的患者不适合免疫治疗，这有助于选择适合免疫治疗的确切患者。遗传和表观遗传因素均影响ANGPT2的表达，其中超级增强子的影响更为显著。本文首次对ANGPT2进行了系统分析，并展示了其在泛癌中的特征。我们总结了ANGPT2在肿瘤诊断和预后中的生物标志物作用，以及其在肿瘤免疫治疗中的靶点作用。
