m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment
BackgroundN6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotic cells. There is accumulating evidence that m6A methylation can play a significant role in the early diagnosis and treatment of cancers. However, the mechanism underlying the involvement of m6A in cervica...
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| Format: | Article |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.888650/full |
| _version_ | 1828498778822279168 |
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| author | Wenyi Zhang Pei Xiao Jiayi Tang Rui Wang Xiangdong Wang Fengxu Wang Junpu Ruan Shali Yu Juan Tang Rongrong Huang Xinyuan Zhao |
| author_facet | Wenyi Zhang Pei Xiao Jiayi Tang Rui Wang Xiangdong Wang Fengxu Wang Junpu Ruan Shali Yu Juan Tang Rongrong Huang Xinyuan Zhao |
| author_sort | Wenyi Zhang |
| collection | DOAJ |
| description | BackgroundN6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotic cells. There is accumulating evidence that m6A methylation can play a significant role in the early diagnosis and treatment of cancers. However, the mechanism underlying the involvement of m6A in cervical cancer remains unclear.MethodsHere, we examined the m6A modification patterns of immune cells in the tumour microenvironments (TMEs) of 306 patients with cervical cancer from The Cancer Genome Atlas dataset and analysed the relations between them according to 32 m6A regulators. Immune infiltration in the TME of cervical cancer was analysed using the CIBERSORT algorithm and single-sample gene set enrichment analysis. The m6Ascore was structured though principal component analysis.ResultsTwo different m6A modification patterns were detected in 306 patients with cervical cancer, designated as m6Acluster A and B. The immune cell infiltration characteristics and biological behaviour differed between the two patterns, with m6Acluster A showing a higher level of immune infiltration. The samples were also divided into two genomic subtypes according to 114 m6A regulatory genes shown to be closely correlated with prognosis on univariate Cox regression analysis. Survival analysis showed that gene cluster B was related to better survival than gene cluster A. Most of the m6A regulators showed higher expression in gene cluster B than in gene cluster A. Single-sample gene set enrichment analysis indicated a higher level of immune cell infiltration in gene cluster A. The m6Ascore signature was examined to determine the m6A modification patterns in cervical cancer. Patients with a high m6Ascore showed better survival, while the low m6Ascore group had a higher mutation frequency and better response to treatment.ConclusionsThis study showed that m6A modification patterns play important roles in cervical cancer. Analysis of m6A modification patterns will yield an improved understanding of the TME in cervical cancer, and facilitate the development of better immunotherapy strategies. |
| first_indexed | 2024-12-11T13:13:13Z |
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| language | English |
| last_indexed | 2024-12-11T13:13:13Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b5baaeb709de4ffc817a74fd53dff79b2022-12-22T01:06:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.888650888650m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer MicroenvironmentWenyi Zhang0Pei Xiao1Jiayi Tang2Rui Wang3Xiangdong Wang4Fengxu Wang5Junpu Ruan6Shali Yu7Juan Tang8Rongrong Huang9Xinyuan Zhao10Department of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaCenter for Non-Communicable Disease Management, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaDepartment of Pharmacy, Affiliated Hospital of Nantong University, Nantong, ChinaDepartment of Occupational Medicine and Environmental Toxicology, Nantong Key Laboratory of Environmental Toxicology, School of Public Health, Nantong University, Nantong, ChinaBackgroundN6-methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotic cells. There is accumulating evidence that m6A methylation can play a significant role in the early diagnosis and treatment of cancers. However, the mechanism underlying the involvement of m6A in cervical cancer remains unclear.MethodsHere, we examined the m6A modification patterns of immune cells in the tumour microenvironments (TMEs) of 306 patients with cervical cancer from The Cancer Genome Atlas dataset and analysed the relations between them according to 32 m6A regulators. Immune infiltration in the TME of cervical cancer was analysed using the CIBERSORT algorithm and single-sample gene set enrichment analysis. The m6Ascore was structured though principal component analysis.ResultsTwo different m6A modification patterns were detected in 306 patients with cervical cancer, designated as m6Acluster A and B. The immune cell infiltration characteristics and biological behaviour differed between the two patterns, with m6Acluster A showing a higher level of immune infiltration. The samples were also divided into two genomic subtypes according to 114 m6A regulatory genes shown to be closely correlated with prognosis on univariate Cox regression analysis. Survival analysis showed that gene cluster B was related to better survival than gene cluster A. Most of the m6A regulators showed higher expression in gene cluster B than in gene cluster A. Single-sample gene set enrichment analysis indicated a higher level of immune cell infiltration in gene cluster A. The m6Ascore signature was examined to determine the m6A modification patterns in cervical cancer. Patients with a high m6Ascore showed better survival, while the low m6Ascore group had a higher mutation frequency and better response to treatment.ConclusionsThis study showed that m6A modification patterns play important roles in cervical cancer. Analysis of m6A modification patterns will yield an improved understanding of the TME in cervical cancer, and facilitate the development of better immunotherapy strategies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.888650/fullm6A regulatorstumour microenvironmentimmunotherapyprognosiscervical cancer |
| spellingShingle | Wenyi Zhang Pei Xiao Jiayi Tang Rui Wang Xiangdong Wang Fengxu Wang Junpu Ruan Shali Yu Juan Tang Rongrong Huang Xinyuan Zhao m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment Frontiers in Immunology m6A regulators tumour microenvironment immunotherapy prognosis cervical cancer |
| title | m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment |
| title_full | m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment |
| title_fullStr | m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment |
| title_full_unstemmed | m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment |
| title_short | m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment |
| title_sort | m6a regulator mediated tumour infiltration and methylation modification in cervical cancer microenvironment |
| topic | m6A regulators tumour microenvironment immunotherapy prognosis cervical cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.888650/full |
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