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Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma
N6-methylandrostenedione (m6A) methylation plays a very important role in the development of malignant tumors. The immune system is the key point in the progression of tumors, particularly in terms of tumor treatment and drug resistance. Tumor immunotherapy has now become a hot spot and a new approa...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291731/ https://www.ncbi.nlm.nih.gov/pubmed/35859893 http://dx.doi.org/10.3389/fcell.2022.935135 |
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author | Luo, Na Fu, Min Zhang, Yiling Li, Xiaoyu Zhu, Wenjun Yang, Feng Chen, Ziqi Mei, Qi Peng, Xiaohong Shen, Lulu Zhang, Yuanyuan Li, Qianxia Hu, Guangyuan |
author_facet | Luo, Na Fu, Min Zhang, Yiling Li, Xiaoyu Zhu, Wenjun Yang, Feng Chen, Ziqi Mei, Qi Peng, Xiaohong Shen, Lulu Zhang, Yuanyuan Li, Qianxia Hu, Guangyuan |
author_sort | Luo, Na |
collection | PubMed |
description | N6-methylandrostenedione (m6A) methylation plays a very important role in the development of malignant tumors. The immune system is the key point in the progression of tumors, particularly in terms of tumor treatment and drug resistance. Tumor immunotherapy has now become a hot spot and a new approach for tumor treatment. However, as far as the stomach adenocarcinoma (STAD) is concerned, the in-depth research is still a gap in the m6A-associated immune markers. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases is extremely important for our research, where we obtained gene mutation, gene expression data and relevant clinical information of STAD patients. Firstly, the samples from GEO were used as external validation groups, while the TCGA samples were divided into a training group and an internal validation group randomly. Using the way of Single factor COX-LASSO- and multi-factor Cox to construct the prognostic model. Then, all samples were subjected to cluster analysis to generate high and low expression groups of immune gene. Meanwhile, we also collected the correlation between these types and tumor microenvironment. On this basis, a web version of the dynamic nomogram APP was developed. In addition, we performed microenvironmental correlation, copy number variation and mutation analyses for model genes. The prognostic model for STAD developed here demonstrated a very strong predictive ability. The results of cluster analysis manifested that the immune gene low expression group had lower survival rate and higher degree of immune infiltration. Therefore, the immune gene low expression group was associated with lower survival rates and a higher degree of immune infiltration. Gene set enrichment analysis suggested that the potential mechanism might be related to the activation of immunosuppressive functions and multiple signaling pathways. Correspondingly, the web version of the dynamic nomogram APP produced by the DynNom package has successfully achieved rapid and accurate calculation of patient survival rates. Finally, the multi-omics analysis of model genes further enriched the research content. Interference of RAB19 was confirmed to facilitate migration of STAD cells in vitro, while its overexpression inhibited these features. The prognostic model for STAD constructed in this study is accurate and efficient based on multi-omics analysis and experimental validation. Additionally, the results of the correlation analysis between the tumor microenvironment and m6Ascore are the basics of further exploration of the pathophysiological mechanism in STAD. |
format | Online Article Text |
id | pubmed-9291731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92917312022-07-19 Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma Luo, Na Fu, Min Zhang, Yiling Li, Xiaoyu Zhu, Wenjun Yang, Feng Chen, Ziqi Mei, Qi Peng, Xiaohong Shen, Lulu Zhang, Yuanyuan Li, Qianxia Hu, Guangyuan Front Cell Dev Biol Cell and Developmental Biology N6-methylandrostenedione (m6A) methylation plays a very important role in the development of malignant tumors. The immune system is the key point in the progression of tumors, particularly in terms of tumor treatment and drug resistance. Tumor immunotherapy has now become a hot spot and a new approach for tumor treatment. However, as far as the stomach adenocarcinoma (STAD) is concerned, the in-depth research is still a gap in the m6A-associated immune markers. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases is extremely important for our research, where we obtained gene mutation, gene expression data and relevant clinical information of STAD patients. Firstly, the samples from GEO were used as external validation groups, while the TCGA samples were divided into a training group and an internal validation group randomly. Using the way of Single factor COX-LASSO- and multi-factor Cox to construct the prognostic model. Then, all samples were subjected to cluster analysis to generate high and low expression groups of immune gene. Meanwhile, we also collected the correlation between these types and tumor microenvironment. On this basis, a web version of the dynamic nomogram APP was developed. In addition, we performed microenvironmental correlation, copy number variation and mutation analyses for model genes. The prognostic model for STAD developed here demonstrated a very strong predictive ability. The results of cluster analysis manifested that the immune gene low expression group had lower survival rate and higher degree of immune infiltration. Therefore, the immune gene low expression group was associated with lower survival rates and a higher degree of immune infiltration. Gene set enrichment analysis suggested that the potential mechanism might be related to the activation of immunosuppressive functions and multiple signaling pathways. Correspondingly, the web version of the dynamic nomogram APP produced by the DynNom package has successfully achieved rapid and accurate calculation of patient survival rates. Finally, the multi-omics analysis of model genes further enriched the research content. Interference of RAB19 was confirmed to facilitate migration of STAD cells in vitro, while its overexpression inhibited these features. The prognostic model for STAD constructed in this study is accurate and efficient based on multi-omics analysis and experimental validation. Additionally, the results of the correlation analysis between the tumor microenvironment and m6Ascore are the basics of further exploration of the pathophysiological mechanism in STAD. Frontiers Media S.A. 2022-06-24 /pmc/articles/PMC9291731/ /pubmed/35859893 http://dx.doi.org/10.3389/fcell.2022.935135 Text en Copyright © 2022 Luo, Fu, Zhang, Li, Zhu, Yang, Chen, Mei, Peng, Shen, Zhang, Li and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Luo, Na Fu, Min Zhang, Yiling Li, Xiaoyu Zhu, Wenjun Yang, Feng Chen, Ziqi Mei, Qi Peng, Xiaohong Shen, Lulu Zhang, Yuanyuan Li, Qianxia Hu, Guangyuan Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma |
title | Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma |
title_full | Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma |
title_fullStr | Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma |
title_full_unstemmed | Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma |
title_short | Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma |
title_sort | prognostic role of m6a-associated immune genes and cluster-related tumor microenvironment analysis: a multi-omics practice in stomach adenocarcinoma |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291731/ https://www.ncbi.nlm.nih.gov/pubmed/35859893 http://dx.doi.org/10.3389/fcell.2022.935135 |
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