Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification

Abstract Background N6-methyladenine (m6A) is the most common modification of mRNA and IncRNA in higher organisms. m6A has been confirmed to be related to the formation and progression of tumors and m6A-related genes can be used as prognostic biomarkers in a variety of tumors. However, there have be...

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Autores principales:	Jialin Qu, Li Wang, Man Jiang, Zhimin Wei, Guangming Fu, Xiaochun Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	N6-methyladenine Prognostic model Lung squamous cell carcinoma Bioinformatic analysis Epigenetics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c26b07adc64247019336178a81d62510
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spelling	oai:doaj.org-article:c26b07adc64247019336178a81d625102021-11-28T12:27:34ZSurvival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification10.1186/s12885-021-08939-61471-2407https://doaj.org/article/c26b07adc64247019336178a81d625102021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08939-6https://doaj.org/toc/1471-2407Abstract Background N6-methyladenine (m6A) is the most common modification of mRNA and IncRNA in higher organisms. m6A has been confirmed to be related to the formation and progression of tumors and m6A-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 m6A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis. Methods We integrated three m6A 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 m6A 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 m6A 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 m6A 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.Jialin QuLi WangMan JiangZhimin WeiGuangming FuXiaochun ZhangBMCarticleN6-methyladeninePrognostic modelLung squamous cell carcinomaBioinformatic analysisEpigeneticsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	N6-methyladenine Prognostic model Lung squamous cell carcinoma Bioinformatic analysis Epigenetics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	N6-methyladenine Prognostic model Lung squamous cell carcinoma Bioinformatic analysis Epigenetics Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jialin Qu Li Wang Man Jiang Zhimin Wei Guangming Fu Xiaochun Zhang Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
description	Abstract Background N6-methyladenine (m6A) is the most common modification of mRNA and IncRNA in higher organisms. m6A has been confirmed to be related to the formation and progression of tumors and m6A-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 m6A-related genes in lung squamous cell carcinoma tissues and its relationship with patient clinical prognosis. Methods We integrated three m6A 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 m6A 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 m6A 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 m6A 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.
format	article
author	Jialin Qu Li Wang Man Jiang Zhimin Wei Guangming Fu Xiaochun Zhang
author_facet	Jialin Qu Li Wang Man Jiang Zhimin Wei Guangming Fu Xiaochun Zhang
author_sort	Jialin Qu
title	Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_short	Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_full	Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_fullStr	Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_full_unstemmed	Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
title_sort	survival-associated n6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
publisher	BMC
publishDate	2021
url	https://doaj.org/article/c26b07adc64247019336178a81d62510
work_keys_str_mv	AT jialinqu survivalassociatedn6adenosinemethyltransferasesignaturesinlungsquamouscellcarcinomaandclinicalverification AT liwang survivalassociatedn6adenosinemethyltransferasesignaturesinlungsquamouscellcarcinomaandclinicalverification AT manjiang survivalassociatedn6adenosinemethyltransferasesignaturesinlungsquamouscellcarcinomaandclinicalverification AT zhiminwei survivalassociatedn6adenosinemethyltransferasesignaturesinlungsquamouscellcarcinomaandclinicalverification AT guangmingfu survivalassociatedn6adenosinemethyltransferasesignaturesinlungsquamouscellcarcinomaandclinicalverification AT xiaochunzhang survivalassociatedn6adenosinemethyltransferasesignaturesinlungsquamouscellcarcinomaandclinicalverification
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Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification

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