m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia
RNA N6-methyladenosine (m6A) is the most common and intensively studied RNA modification that critically regulates RNA metabolism, cell signaling, cell survival, and differentiation. However, the overall role of multiple m6A regulators in the tumor microenvironment (TME) has not yet been fully eluci...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.948079/full |
| _version_ | 1811341707799691264 |
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| author | Zi-Jun Xu Zi-Jun Xu Zi-Jun Xu Xiang-Mei Wen Xiang-Mei Wen Xiang-Mei Wen Yuan-Cui Zhang Ye Jin Ye Jin Ji-Chun Ma Ji-Chun Ma Ji-Chun Ma Yu Gu Yu Gu Xin-Yi Chen Xin-Yi Chen Xin-Yi Chen Pei-Hui Xia Pei-Hui Xia Pei-Hui Xia Wei Qian Jiang Lin Jiang Lin Jiang Lin Jun Qian Jun Qian |
| author_facet | Zi-Jun Xu Zi-Jun Xu Zi-Jun Xu Xiang-Mei Wen Xiang-Mei Wen Xiang-Mei Wen Yuan-Cui Zhang Ye Jin Ye Jin Ji-Chun Ma Ji-Chun Ma Ji-Chun Ma Yu Gu Yu Gu Xin-Yi Chen Xin-Yi Chen Xin-Yi Chen Pei-Hui Xia Pei-Hui Xia Pei-Hui Xia Wei Qian Jiang Lin Jiang Lin Jiang Lin Jun Qian Jun Qian |
| author_sort | Zi-Jun Xu |
| collection | DOAJ |
| description | RNA N6-methyladenosine (m6A) is the most common and intensively studied RNA modification that critically regulates RNA metabolism, cell signaling, cell survival, and differentiation. However, the overall role of multiple m6A regulators in the tumor microenvironment (TME) has not yet been fully elucidated in acute myeloid leukemia (AML). In our study, we explored the genetic and transcriptional alterations of 23 m6A regulators in AML patients. Three distinct molecular subtypes were identified and associated with prognosis, patient clinicopathological features, as well as TME characteristics. The TME characterization revealed that m6A patterns were highly connected with metabolic pathways such as biosynthesis of unsaturated fatty acids, cysteine and methionine metabolism, and citrate cycle TCA cycle. Then, based on the differentially expressed genes (DEGs) related to m6A molecular subtypes, our study categorized the entire cohort into three m6A gene clusters. Furthermore, we constructed the m6Ascore for quantification of the m6A modification pattern of individual AML patients. It was found that the tumor-infiltrating lymphocyte cells (TILs) closely correlated with the three m6A clusters, three m6A gene clusters, and m6Ascore. And many biological processes were involved, including glycogen degradation, drug metabolism by cytochrome P450, pyruvate metabolism, and so on. Our comprehensive analysis of m6A regulators in AML demonstrated their potential roles in the clinicopathological features, prognosis, tumor microenvironment, and particularly metabolic pathways. These findings may improve our understanding of m6A regulators in AML and offer new perspectives on the assessment of prognosis and the development of anticancer strategy. |
| first_indexed | 2024-04-13T18:57:55Z |
| format | Article |
| id | doaj.art-1aba518a7f2041a793accea473e1b81f |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T18:57:55Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-1aba518a7f2041a793accea473e1b81f2022-12-22T02:34:10ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.948079948079m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemiaZi-Jun Xu0Zi-Jun Xu1Zi-Jun Xu2Xiang-Mei Wen3Xiang-Mei Wen4Xiang-Mei Wen5Yuan-Cui Zhang6Ye Jin7Ye Jin8Ji-Chun Ma9Ji-Chun Ma10Ji-Chun Ma11Yu Gu12Yu Gu13Xin-Yi Chen14Xin-Yi Chen15Xin-Yi Chen16Pei-Hui Xia17Pei-Hui Xia18Pei-Hui Xia19Wei Qian20Jiang Lin21Jiang Lin22Jiang Lin23Jun Qian24Jun Qian25Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaThe Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaLaboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaThe Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Internal Medicine, The Affiliated Third Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaLaboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaThe Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaLaboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaThe Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaLaboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaThe Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaLaboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaThe Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaZhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaDepartment of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, ChinaRNA N6-methyladenosine (m6A) is the most common and intensively studied RNA modification that critically regulates RNA metabolism, cell signaling, cell survival, and differentiation. However, the overall role of multiple m6A regulators in the tumor microenvironment (TME) has not yet been fully elucidated in acute myeloid leukemia (AML). In our study, we explored the genetic and transcriptional alterations of 23 m6A regulators in AML patients. Three distinct molecular subtypes were identified and associated with prognosis, patient clinicopathological features, as well as TME characteristics. The TME characterization revealed that m6A patterns were highly connected with metabolic pathways such as biosynthesis of unsaturated fatty acids, cysteine and methionine metabolism, and citrate cycle TCA cycle. Then, based on the differentially expressed genes (DEGs) related to m6A molecular subtypes, our study categorized the entire cohort into three m6A gene clusters. Furthermore, we constructed the m6Ascore for quantification of the m6A modification pattern of individual AML patients. It was found that the tumor-infiltrating lymphocyte cells (TILs) closely correlated with the three m6A clusters, three m6A gene clusters, and m6Ascore. And many biological processes were involved, including glycogen degradation, drug metabolism by cytochrome P450, pyruvate metabolism, and so on. Our comprehensive analysis of m6A regulators in AML demonstrated their potential roles in the clinicopathological features, prognosis, tumor microenvironment, and particularly metabolic pathways. These findings may improve our understanding of m6A regulators in AML and offer new perspectives on the assessment of prognosis and the development of anticancer strategy.https://www.frontiersin.org/articles/10.3389/fgene.2022.948079/fullm6Aacute myeloid leukemiatumor microenvironmentimmune infiltrationmetabolic pathways |
| spellingShingle | Zi-Jun Xu Zi-Jun Xu Zi-Jun Xu Xiang-Mei Wen Xiang-Mei Wen Xiang-Mei Wen Yuan-Cui Zhang Ye Jin Ye Jin Ji-Chun Ma Ji-Chun Ma Ji-Chun Ma Yu Gu Yu Gu Xin-Yi Chen Xin-Yi Chen Xin-Yi Chen Pei-Hui Xia Pei-Hui Xia Pei-Hui Xia Wei Qian Jiang Lin Jiang Lin Jiang Lin Jun Qian Jun Qian m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia Frontiers in Genetics m6A acute myeloid leukemia tumor microenvironment immune infiltration metabolic pathways |
| title | m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia |
| title_full | m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia |
| title_fullStr | m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia |
| title_full_unstemmed | m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia |
| title_short | m6A regulator-based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia |
| title_sort | m6a regulator based methylation modification patterns and characterization of tumor microenvironment in acute myeloid leukemia |
| topic | m6A acute myeloid leukemia tumor microenvironment immune infiltration metabolic pathways |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.948079/full |
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