METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker
Methyltransferase-like 3 (METTL3) 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 METTL3 in esopha...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.824190/full |
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| author | Yubin Zhou Songhe Guo Yiqiu Li Fangfang Chen Yaxian Wu Yi Xiao Jun An |
| author_facet | Yubin Zhou Songhe Guo Yiqiu Li Fangfang Chen Yaxian Wu Yi Xiao Jun An |
| author_sort | Yubin Zhou |
| collection | DOAJ |
| description | Methyltransferase-like 3 (METTL3) 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 METTL3 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, https://www.immport.org/home) provided 2483 immune-related genes. METTL3 was substantially expressed in ESCC and linked to poor prognosis in ESCC, according to the findings. Functional analysis revealed that METTL3 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 METTL3 expression. We screened immune genes associated with METTL3 by Spearman’s analysis and performed functional analysis. These immune genes were mostly linked with immune processes, such as cytokine receptors, the MAPK signaling pathway, and natural killer cell-mediated cytotoxicity, indicating that METTL3 is a key molecule in the immune regulation of esophageal cancer. In addition, based on METTL3-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 METTL3 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. |
| first_indexed | 2024-04-14T05:49:02Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-14T05:49:02Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj.art-ee5acc087c334ce0a3284e9cc55573ed2022-12-22T02:09:11ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.824190824190METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy BiomarkerYubin Zhou0Songhe Guo1Yiqiu Li2Fangfang Chen3Yaxian Wu4Yi Xiao5Jun An6Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Clinical Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaDepartment of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaDepartment of Clinical Laboratory, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaDepartment of Cardiothoracic Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, ChinaMethyltransferase-like 3 (METTL3) 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 METTL3 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, https://www.immport.org/home) provided 2483 immune-related genes. METTL3 was substantially expressed in ESCC and linked to poor prognosis in ESCC, according to the findings. Functional analysis revealed that METTL3 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 METTL3 expression. We screened immune genes associated with METTL3 by Spearman’s analysis and performed functional analysis. These immune genes were mostly linked with immune processes, such as cytokine receptors, the MAPK signaling pathway, and natural killer cell-mediated cytotoxicity, indicating that METTL3 is a key molecule in the immune regulation of esophageal cancer. In addition, based on METTL3-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 METTL3 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.824190/fullesophageal squamous cell carcinomaMETTL3m6A modificationimmune infiltrationimmunotypingprognostic model |
| spellingShingle | Yubin Zhou Songhe Guo Yiqiu Li Fangfang Chen Yaxian Wu Yi Xiao Jun An METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker Frontiers in Oncology esophageal squamous cell carcinoma METTL3 m6A modification immune infiltration immunotyping prognostic model |
| title | METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker |
| title_full | METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker |
| title_fullStr | METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker |
| title_full_unstemmed | METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker |
| title_short | METTL3 Is Associated With the Malignancy of Esophageal Squamous Cell Carcinoma and Serves as a Potential Immunotherapy Biomarker |
| title_sort | mettl3 is associated with the malignancy of esophageal squamous cell carcinoma and serves as a potential immunotherapy biomarker |
| topic | esophageal squamous cell carcinoma METTL3 m6A modification immune infiltration immunotyping prognostic model |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.824190/full |
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