An integrated model of FTO and METTL3 expression that predicts prognosis in lung squamous cell carcinoma patients

Abstract

Background: Lung squamous cell carcinoma (LUSC) approximately accounts for a third of lung cancers.However, the role of N6-methyladenosine (m6A) in LUSC remains largely unknown according to previous studies. Methods:In this study, we investigated the mutations, copy number variants (CNVs), expression of 20 m6A RNA methylation regulators, and clinical data from The Cancer Genome Atlas-LUSC (TCGA-LUSC). These data were used for the training cohort of screening potential biomarkers. The prognostic model of m6A RNA methylation regulators was constructed. A receiver operating characteristic (ROC) analysis was undertaken to determine the area under the curves (AUCs) (for 3-and 5-year survival) for the model. Additionally, the accuracy of the two-gene model was confirmed with external data verifications.Combined two-gene model and clinincal information were performed to construct a nomogram to predict patient's prognostic risk assessment.Results: Fat mass-and obesity-associated protein (FTO) and methyltransferase-like 3 (METTL3) were identified as potential prognostic biomarkers to evaluate benign and malignant tumors and prognosticate.The following prognostic model of m6A RNA methylation regulators was constructed: risk score = 0.162 × FTO − 0.069 × METTL3. Patients in low-risk group [median overall survival (mOS), 43.4 months] had longer survival than those with high-risk (mOS, 67.3 months) with P=0.0023. The smoking grade and risk score could be independent prognostic factors (P=0.00098 and P=0.0014, respectively). Ultimately, a nomogram was developed to assist clinicians to predict clinical outcomes.Conclusions: FTO and METTL3 are potential prognostic biomarkers of LUSC. The two-gene model's use of prognostic risk scores may provide guidance in the selection of therapeutic strategies.

A Novel Prognosis Signature Based on Ferroptosis-Related Gene DNA Methylation Data for Lung Squamous Cell Carcinoma

“…e risk prognosis model based on 31 methylation sites of FRGs was superior to the model based on clinicopathologic features in the prediction of 1-, 3-, 5-, and 10-year OS in LUSC. In addition, the accuracy and efficiency of this risk prognosis model were significantly superior to other published models [17,18,[27][28][29][30][31] for LUSC patients.…”

“…In addition, the nomogram was tested by proportional hazard assumption to analyze that whether the risk score included in our model was independent prognostic indicators. To evaluate the accuracy and effectiveness of our model, 7 prognostic models of LUSC from published papers [17,18,[27][28][29][30][31] were reviewed and studied with a comparison. Net reclassification index (NRI) and integrated discrimination improvement (IDI) are the common algorithms used to assess the model in recent years [32,33].…”

The role of m6A demethylases in lung cancer: diagnostic and therapeutic implications

“…Recent research has focused on the construction of such models using factors including FTO and other genes. For instance, Zhang et al developed a model, and found that a two-gene model combining FTO and METTL3 was more effective in guiding prognostic assessment of lung cancer (66). Additionally, researchers have utilized methylation-related enzymes such as FTO and ALKBH5 to develop risk assessment models for LUAD patients.…”

Economic evaluation of cemiplimab plus chemotherapy regimen for advanced non-small-cell lung cancer

“…Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases and encompasses various histological subtypes, including adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma [ 3 ]. Among these subtypes, squamous cell carcinoma accounts for approximately 30% [ 4 , 5 ]. Due to the absence of noticeable symptoms and effective screening methods, lung cancer is often diagnosed at advanced or metastatic stages, resulting in poor long-term prognosis [ 6 ].…”