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Updated: Oct 12, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Survival-associated N6-adenosine methyltransferase signatures in lung squamous cell carcinoma and clinical
Jialin Qu1, Li Wang2, Man Jiang3
1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250117, China.
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.
Insights
N⁶-methyladenine (m⁶A) modification is crucial in cancer. This study reveals METTL3 gene expression as a key prognostic factor for lung squamous cell carcinoma, offering potential for improved patient assessment and treatment.
Area of Science:
- Epigenetics
- Molecular Oncology
Background:
- N⁶-methyladenine (m⁶A) is the most prevalent mRNA modification in eukaryotes.
- m⁶A dysregulation is implicated in various cancers, but its role in lung squamous cell carcinoma (LUSC) remains understudied.
Purpose of the Study:
- To investigate the differential expression of m⁶A-related genes in LUSC.
- To explore the relationship between m⁶A gene expression and patient prognosis in LUSC.
Main Methods:
- Integrated data from TCGA and GEO databases for LUSC patients.
- Developed a risk-prognosis model based on m⁶A methylase gene expression.
- Validated findings using principal component analysis, ROC curve analysis, and immunohistochemistry.
Main Results:
- Significant differences in m⁶A methylase expression between LUSC tumor and normal tissues were observed.
- A prognostic model based on METTL3 gene expression demonstrated predictive performance (AUC: 0.706).
- High METTL3 expression correlated with improved survival rates in LUSC patients.
Conclusions:
- METTL3 expression serves as an independent prognostic factor for LUSC.
- m⁶A methylases play a significant role in LUSC development and progression.
- Findings may guide personalized prognostic assessment and treatment strategies for LUSC.
