Abstract
BackgroundN6-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.MethodsWe 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.ResultsThe 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.ConclusionsOur 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.
Highlights
Lung cancer is the malignant tumor with the highest incidence and fatality rate in the world
A variety of driver gene mutations such as EGFR, BRAF, ERBB2 or rearrangement of ALK or ROS1 are found in lung adenocarcinoma and the corresponding small molecule tyrosine kinase inhibitors (TKIs) have been put into clinical application, which prolong the median survival of patients with advanced lung adenocarcinoma [3]
The m6A methyltransferase gene shows a significant expression difference between lung squamous cell carcinoma and normal tissues According to the RNA-seq transcriptome data from the The Cancer Genome Atlas (TCGA) database, we analyzed the expression levels of m6A methyltransferase genes from tumor and normal tissues
Summary
Lung cancer is the malignant tumor with the highest incidence and fatality rate in the world. Lung squamous cell carcinoma, which accounts for 40 to 51% of nonsmall cell lung cancers, lacks driver gene mutations that can be used as drug targets. In the context of the continuous updating of tumor treatment and improvement of survival rates, lung squamous cell carcinoma has not made breakthrough progress in decades except immunotherapy and its 5-year survival rate is only 5% [5]. 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. 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. Immunohistochemistry revealed that patients with high METTL3 expression exhibited a longer survival time than those with low METTL3 expression
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