The role of Myocyte Enhancer Factor 2 C (MEF2C) in lung adenocarcinoma (LUAD) is unclear. To address this gap in knowledge, we employed bioinformatics analysis and experimental validation in this study. This study investigated MEF2C expression across a spectrum of cancers, with a specific focus on lung adenocarcinoma (LUAD), utilizing Cancer Genome Atlas (TCGA) data to assess its potential as a diagnostic marker. The study also investigated correlations between MEF2C expression and clinical traits and prognostic indicators of LUAD. Additionally, this study also delved into the regulatory mechanisms of MEF2C, examining its connections to immune system interactions, immune checkpoint genes, tumor mutational burden (TMB), and the sensitivity of LUAD to various drugs. Through single-cell sequencing of LUAD cells and genetic variation of MEF2C in LUAD, we explored the expression of MEF2C in cell lines and verified it by quantitative real-time PCR (qRT-PCR). MEF2C exhibited aberrant expression in both pan-cancer and LUAD. In individuals with LUAD, diminished levels of MEF2C expression were notably linked to the effectiveness of primary therapy outcome (p = 0.025), gender (p < 0.001), and the subdivision of anatomic neoplasms 2 (p = 0.011). A decline in MEF2C levels was also found to be significantly related to reduced overall survival (OS) in LUAD patients (p = 0.026). The presence of MEF2C was recognized as a standalone factor predictive of prognosis in LUAD (p = 0.029). MEF2C was found to be involved in multiple biological pathways, such as those involving cell adhesion molecules. Additionally, its expression was correlated with the extent of immune cell presence, the activity of immune checkpoint genes, and TMB in LUAD. Notably, an inverse relationship was observed between MEF2C expression and the sensitivity to several agents, including Topotecan, Irinotecan, Panobinostat, Nilotinib, and Tp38-279, within the context of LUAD. Furthermore, MEF2C was found to be significantly negatively regulated in LUAD cell lines. The results imply that MEF2C could be a valuable indicator for predicting outcomes and a possible target for immunotherapy for LUAD patients.
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