دورية أكاديمية
Use of Novel m6A Regulator-mediated Methylation Modification Patterns in Distinct Tumor Microenvironment Profiles to Identify and Predict Glioma Prognosis and Progression, T-cell Dysfunction, and Clinical Response to ICI Immunotherapy
| العنوان: | Use of Novel m6A Regulator-mediated Methylation Modification Patterns in Distinct Tumor Microenvironment Profiles to Identify and Predict Glioma Prognosis and Progression, T-cell Dysfunction, and Clinical Response to ICI Immunotherapy |
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| المؤلفون: | Zhang, Wenxiong, Zhao, Binghao, Xiang, Zhongtian, Wu, Bo, Zhang, Xiang, Feng, Nan, Wei, Yiping |
| المساهمون: | National Natural Science Foundation of China, Natural Science Foundation of Jiangxi Province |
| المصدر: | Current Pharmaceutical Design ; volume 29, issue 1, page 60-78 ; ISSN 1381-6128 |
| بيانات النشر: | Bentham Science Publishers Ltd. |
| سنة النشر: | 2023 |
| الوصف: | Background: The specific functions of RNA N6-methyladenosine (m6A) modifications in the glioma tumor microenvironment (TME) and glioma patient prognosis and treatment have not been determined to date. Objective: The objective of the study was to determine the role of m6A modifications in glioma TME. Methods: Nonnegative matrix factorization (NMF) methods were used to determine m6A clusters and m6A gene signatures based on 21 genes relating to m6A modifications. TME characteristics for each m6A cluster and m6A gene signature were quantified by established m6A score. The utility of m6A score was validated in immunotherapy and other antiangiogenic treatment cohorts. Results: Three m6A clusters were identified among 3,395 glioma samples, and they were linked to different biological activities and clinical outcomes. The m6A clusters were highly consistent with immune profiles known as immune-inflamed, immune-excluded, and immune-desert phenotypes. Clusters within individual tumors could predict glioma inflammation, molecular subtypes, TME stromal activity, genetic variation, alternative splicing, and prognosis. As for the m6A score and m6A gene signature, patients with low m6A scores exhibited an increased tumor mutation burden, immune activity, neoantigen load, and prolonged survival. A low m6A score indicated the potential for a low level of T-cell dysfunction, a considerably better treatment response, and durable clinical benefits from immunotherapy, bevacizumab and regorafenib. Conclusion: Glioma m6A clusters and gene signatures have distinctive TME features. The m6A gene signature may guide prognostic assessments and promote the use of effective strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.2174/1381612829666221207112438 |
| الإتاحة: | https://doi.org/10.2174/1381612829666221207112438Test https://www.eurekaselect.com/211684/articleTest |
| رقم الانضمام: | edsbas.8F96FF2D |
| قاعدة البيانات: | BASE |
| DOI: | 10.2174/1381612829666221207112438 |
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