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BMC Cancer

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Open Access 01-12-2021 | Epigenetics | Research

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

Authors: Jialin Qu, Li Wang, Man Jiang, Zhimin Wei, Guangming Fu, Xiaochun Zhang

Published in: BMC Cancer | Issue 1/2021

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.

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Title: Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical verification
Authors: Jialin Qu
Li Wang
Man Jiang
Zhimin Wei
Guangming Fu
Xiaochun Zhang
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Epigenetics
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08939-6

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