{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T16:26:28Z","timestamp":1777479988399,"version":"3.51.4"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Methyltransferase-like 3 (<jats:italic>METTL3<\/jats:italic>) is an RNA methyltransferase mediating N6 methyladenosine (m6A) modification. Its role in cancer pathogenesis and progression has attracted increasing attention. However, the immunological role, possible immune mechanism, and clinical significance of <jats:italic>METTL3<\/jats:italic> in esophageal squamous cell carcinoma (ESCC) remain to be confirmed. The Tumor Genome Atlas (TCGA) provided clinical and transcriptome sequencing data for this study (162 tumor tissue samples and 11 normal tissue samples), while the Immunology Database and Analysis Portal (immport, <jats:uri>https:\/\/www.immport.org\/home<\/jats:uri>) provided 2483 immune-related genes. <jats:italic>METTL3<\/jats:italic> was substantially expressed in ESCC and linked to poor prognosis in ESCC, according to the findings. Functional analysis revealed that <jats:italic>METTL3<\/jats:italic> is mainly involved in chromosomal homologous recombination and DNA mismatch repair processes, which could be potential mechanisms for tumor disease development and progression. Analysis on the TISIDB website shows that effector memory CD8 T cells, NK cells, neutrophils and other cells are highly correlated with <jats:italic>METTL3<\/jats:italic> expression. We screened immune genes associated with <jats:italic>METTL3<\/jats:italic> by Spearman\u2019s analysis and performed functional analysis. These immune genes were mostly linked with immune processes, such as cytokine receptors, the <jats:italic>MAPK<\/jats:italic> signaling pathway, and natural killer cell-mediated cytotoxicity, indicating that <jats:italic>METTL3<\/jats:italic> is a key molecule in the immune regulation of esophageal cancer. In addition, based on <jats:italic>METTL3<\/jats:italic>-related immune genes, we separated the patients into several subgroups and constructed a prognostic prediction model consisting of six immune genes. As an independent prognostic indicator for ESCC, the risk score of this model can be employed. A nomogram was also developed to accurately evaluate individual prognoses based on clinical indicators and risk scores. In summary, this study suggests that <jats:italic>METTL3<\/jats:italic> is not only a potential pathogenic molecule for esophageal carcinogenesis and progression but also a potential biological marker for forecasting ESCC patient prognosis and could serve as a basis for clinical decision making.<\/jats:p>","DOI":"10.3389\/fonc.2022.824190","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T06:08:34Z","timestamp":1651039714000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy 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