Consensus clustering and novel risk score model construction based on m6A methylation regulators to evaluate the prognosis and tumor immune microenvironment of early-stage lung adenocarcinoma

• Published in: Aging (Albany, NY.) Vol. 16; no. 14; pp. 11318 - 11338
• Main Authors: He, Miao, Zhi, Yuxue, Li, Chao, Zhao, Changming, Yang, Guangquan, Lv, Jing, You, Hong, Huang, Hai, Cao, Xiaoyu
• Format: Journal Article
• Language: English
• Published: United States 05.07.2024
• Subjects: Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Adenosine - analogs & derivatives; Adenosine - genetics; Adenosine - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell Line, Tumor; Cluster Analysis; Female; Gene Expression Regulation, Neoplastic; Heterogeneous-Nuclear Ribonucleoprotein Group C - genetics; Heterogeneous-Nuclear Ribonucleoprotein Group C - metabolism; Humans; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Methylation; Middle Aged; Neoplasm Staging; Prognosis; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; early-stage lung adenocarcinoma; m6A methylation regulators; prognostic model; tumor immune microenvironment; risk score
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.206004

The aim of this study was to investigate the correlation between m A methylation regulators and cell infiltration characteristics in tumor immune microenvironment (TIME), so as to help understand the immune mechanism of early-stage lung adenocarcinoma (LUAD). The expression and consensus cluster analyses of m A methylation regulators in early-stage LUAD were performed. The clinicopathological features, immune cell infiltration, survival and functional enrichment in different subtypes were analyzed. We also constructed a prognostic model. Clinical tissue samples were used to validate the expression of model genes through real-time polymerase chain reaction (RT-PCR). In addition, cell scratch assay and Transwell assay were also performed. Expression of m A methylation regulators was abnormal in early-stage LUAD. According to the consensus clustering of m A methylation regulators, patients with early-stage LUAD were divided into two subtypes. Two subtypes showed different infiltration levels of immune cell and survival time. A prognostic model consisting of HNRNPC, IGF2BP1 and IGF2BP3 could be used to predict the survival of early-stage LUAD. RT-PCR results showed that HNRNPC, IGF2BP1 and IGF2BP3 were significantly up-regulated in early-stage LUAD tissues. The results of cell scratch assay and Transwell assay showed that overexpression of HNRNPC promotes the migration and invasion of NCI-H1299 cells, while knockdown HNRNPC inhibits the migration and invasion of NCI-H1299 cells. This work reveals that m A methylation regulators may be potential biomarkers for prognosis in patients with early-stage LUAD. Our prognostic model may be of great value in predicting the prognosis of early-stage LUAD.