Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;29(1):60-78.
doi: 10.2174/1381612829666221207112438.

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

Binghao Zhao  1   2   3   4 , Zhongtian Xiang  1 , Bo Wu  1 , Xiang Zhang  1 , Nan Feng  1 , Yiping Wei  1 , Wenxiong Zhang  1
Affiliations

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

Binghao Zhao et al. Curr Pharm Des. 2023.

Abstract

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.

Keywords: Glioma; immunotherapy; m6A modification; m6A score; multiomics scale; targeted therapy; tumor microenvironment.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Boccaletto P.; Machnicka M.A.; Purta E.; Piątkowski P.; Bagiński B.; Wirecki T.K.; de Crécy-Lagard V.; Ross R.; Limbach P.A.; Kotter A.; Helm M.; Bujnicki J.M.; MODOMICS: A database of RNA modification pathways. 2017 update. Nucleic Acids Res 2018,46(D1),D303-D307 - DOI - PubMed
    1. Cohn W.E.; Pseudouridine, a carbon-carbon linked ribonucleoside in ribonucleic acids: Isolation, structure, and chemical characteristics. J Biol Chem 1960,235(5),1488-1498 - DOI - PubMed
    1. He L.; Li H.; Wu A.; Peng Y.; Shu G.; Yin G.; Functions of N6-methyladenosine and its role in cancer. Mol Cancer 2019,18(1),176 - DOI - PubMed
    1. Chen X.Y.; Zhang J.; Zhu J.S.; The role of m6A RNA methylation in human cancer. Mol Cancer 2019,18(1),103 - DOI - PubMed
    1. Davalos V.; Blanco S.; Esteller M.; SnapShot: Messenger RNA Modifications. Messenger RNA Modifications Cell 2018,174(2),498-498.e1 - PubMed

Publication types

LinkOut - more resources