M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma
N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism...
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Taylor & Francis Group
2024-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2024.2333590 |
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| author | Yong Wang Lisha Peng Feng Wang |
| author_facet | Yong Wang Lisha Peng Feng Wang |
| author_sort | Yong Wang |
| collection | DOAJ |
| description | N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan–Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to anti-PD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity. |
| format | Article |
| id | doaj-art-9dbb16d3c5244ffdb7f21acf9f953c94 |
| institution | Kabale University |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-9dbb16d3c5244ffdb7f21acf9f953c942024-12-13T06:53:25ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2333590M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinomaYong Wang0Lisha Peng1Feng Wang2Department of Radiotherapy, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Radiotherapy, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, ChinaN6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan–Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to anti-PD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity.https://www.tandfonline.com/doi/10.1080/15384047.2024.2333590M6A modificationtumor microenvironmentmolecular patternprognosisnasopharyngeal carcinoma |
| spellingShingle | Yong Wang Lisha Peng Feng Wang M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma Cancer Biology & Therapy M6A modification tumor microenvironment molecular pattern prognosis nasopharyngeal carcinoma |
| title | M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma |
| title_full | M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma |
| title_fullStr | M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma |
| title_full_unstemmed | M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma |
| title_short | M6A-mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma |
| title_sort | m6a mediated molecular patterns and tumor microenvironment infiltration characterization in nasopharyngeal carcinoma |
| topic | M6A modification tumor microenvironment molecular pattern prognosis nasopharyngeal carcinoma |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2024.2333590 |
| work_keys_str_mv | AT yongwang m6amediatedmolecularpatternsandtumormicroenvironmentinfiltrationcharacterizationinnasopharyngealcarcinoma AT lishapeng m6amediatedmolecularpatternsandtumormicroenvironmentinfiltrationcharacterizationinnasopharyngealcarcinoma AT fengwang m6amediatedmolecularpatternsandtumormicroenvironmentinfiltrationcharacterizationinnasopharyngealcarcinoma |