Pan-cancer analysis reveals the prognostic and immunomodulatory potential of super-enhancer-induced ANGPT2 and experimental validation in colorectal cancer.
Songyue Guo, Yanan Yu, Yulan Bu, Jiao Ren, Lu Zhang, Xiaolin Ma, Jiaqiu Li, Ao Li, Xinling Liu
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Abstract
Background: ANGPT2 plays important roles in cancer development. However, there is still no systematic analysis of ANGPT2 in pan-cancer.
Methods: 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.
Results: 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.
Conclusion: 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.
期刊介绍：
Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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