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Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification

BACKGROUND: N(6)-methyladenine (m(6)A) is the most common modification of mRNA and IncRNA in higher organisms. m(6)A has been confirmed to be related to the formation and progression of tumors and m(6)A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have be...

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Autores principales: Qu, Jialin, Wang, Li, Jiang, Man, Wei, Zhimin, Fu, Guangming, Zhang, Xiaochun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611943/
https://www.ncbi.nlm.nih.gov/pubmed/34814861
http://dx.doi.org/10.1186/s12885-021-08939-6
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author Qu, Jialin
Wang, Li
Jiang, Man
Wei, Zhimin
Fu, Guangming
Zhang, Xiaochun
author_facet Qu, Jialin
Wang, Li
Jiang, Man
Wei, Zhimin
Fu, Guangming
Zhang, Xiaochun
author_sort Qu, Jialin
collection PubMed
description BACKGROUND: N(6)-methyladenine (m(6)A) is the most common modification of mRNA and IncRNA in higher organisms. m(6)A has been confirmed to be related to the formation and progression of tumors and m(6)A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have been no similar studies on lung squamous cell carcinoma. The main purpose of this study was aimed to explore the differential expression of m(6)A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis. METHODS: We integrated three m(6)A writers that catalyze the methylation of adenine on mRNA molecules. The training set including 501 patients with LUSC was collected from The Cancer Genome Atlas (TCGA) database and the test set including 181 patients with LUSC was collected from the Gene Expression Omnibus (GEO) database. Based on the expression level of the m(6)A methylase gene, we established a tumor subgroup and risk-prognosis model to quantify the risk index and long-term patient prognosis, which were confirmed by principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis. After lung squamous cell carcinoma tissue specimens were obtained during surgery, immunohistochemistry (IHC) was used to verify the results in vitro. RESULTS: The results of the study showed that the expression of the three m(6)A methylases in tumor tissues and normal tissues was significantly different (P < 0.05). The survival-prognostic model based on METTL3 gene expression showed better predictive performance (AUC: 0.706). Patients in the high-risk and low-risk groups exhibited significant differences in terms of survival time and 5-year and 10-year survival rates. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression. CONCLUSIONS: Our study showed that the molecular phenotype based on the expression of METTL3 may be an independent risk factor affecting the prognosis of lung squamous cell carcinoma. These findings not only prove the important role of m(6)A methylase in lung squamous cell carcinoma, but are also expected to provide more accurate prognostic assessment and individualized treatment for patients with lung squamous cell carcinoma.
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spelling pubmed-86119432021-11-29 Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification Qu, Jialin Wang, Li Jiang, Man Wei, Zhimin Fu, Guangming Zhang, Xiaochun BMC Cancer Research BACKGROUND: N(6)-methyladenine (m(6)A) is the most common modification of mRNA and IncRNA in higher organisms. m(6)A has been confirmed to be related to the formation and progression of tumors and m(6)A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have been no similar studies on lung squamous cell carcinoma. The main purpose of this study was aimed to explore the differential expression of m(6)A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis. METHODS: We integrated three m(6)A writers that catalyze the methylation of adenine on mRNA molecules. The training set including 501 patients with LUSC was collected from The Cancer Genome Atlas (TCGA) database and the test set including 181 patients with LUSC was collected from the Gene Expression Omnibus (GEO) database. Based on the expression level of the m(6)A methylase gene, we established a tumor subgroup and risk-prognosis model to quantify the risk index and long-term patient prognosis, which were confirmed by principal component analysis (PCA) and receiver operating characteristic (ROC) curve analysis. After lung squamous cell carcinoma tissue specimens were obtained during surgery, immunohistochemistry (IHC) was used to verify the results in vitro. RESULTS: The results of the study showed that the expression of the three m(6)A methylases in tumor tissues and normal tissues was significantly different (P < 0.05). The survival-prognostic model based on METTL3 gene expression showed better predictive performance (AUC: 0.706). Patients in the high-risk and low-risk groups exhibited significant differences in terms of survival time and 5-year and 10-year survival rates. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression. CONCLUSIONS: Our study showed that the molecular phenotype based on the expression of METTL3 may be an independent risk factor affecting the prognosis of lung squamous cell carcinoma. These findings not only prove the important role of m(6)A methylase in lung squamous cell carcinoma, but are also expected to provide more accurate prognostic assessment and individualized treatment for patients with lung squamous cell carcinoma. BioMed Central 2021-11-24 /pmc/articles/PMC8611943/ /pubmed/34814861 http://dx.doi.org/10.1186/s12885-021-08939-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Qu, Jialin
Wang, Li
Jiang, Man
Wei, Zhimin
Fu, Guangming
Zhang, Xiaochun
Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_full Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_fullStr Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_full_unstemmed Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_short Survival-associated N(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_sort survival-associated n(6)-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611943/
https://www.ncbi.nlm.nih.gov/pubmed/34814861
http://dx.doi.org/10.1186/s12885-021-08939-6
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