A Comprehensive Bioinformatic Analysis Based on Functional Studies of MEF-2 Family in NSCLC

Yanping Wang; Gaoyang Lin; Wenwen Li; Xue Zhu; Zhentong Zhao; Quanxin Wang

doi:10.59249/PMMF2985

A Comprehensive Bioinformatic Analysis Based on Functional Studies of MEF-2 Family in NSCLC

Yale J Biol Med. 2025 Jun 30;98(2):117-134. doi: 10.59249/PMMF2985. eCollection 2025 Jun.

Authors

Yanping Wang¹, Gaoyang Lin², Wenwen Li³, Xue Zhu², Zhentong Zhao², Quanxin Wang⁴

Affiliations

¹ Department of Paediatrics, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, China.
² Department of Cardiothoracic Surgery, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, China.
³ Department of Gastroenterology, Affiliated Hospital of Weifang Medical College, Weifang, China.
⁴ Department of Ultrasound Diagnosis, Jinan 5th People's Hospital, Jinan, China.

Abstract

Lung cancer remains the malignancy with the highest morbidity and mortality worldwide. There are no effective guiding therapies and prognosis biomarkers, and the overall prognosis of lung cancer remains poor. The cardiomyocyte enhancer factor 2 (MEF-2) family is a highly evolutionarily conserved transcription factor that plays important roles in a variety of diseases, including tumors. Still, the overall bioinformatics function of the MEF-2 gene family in non-small cell lung cancer (NSCLC) has not been systematically reported yet. MEF-2 family members have low expression in NSCLC tissues and are associated with clinicopathological stages. MEF-2B/2D is highly expressed in lung metastatic tissues. MEF-2A, MEF-2B, and MEF-2D have obvious advantages in the diagnosis of NSCLC. Survival analysis of lung adenocarcinoma (LUAD) patients in the Cancer Genome Atlas (TCGA) database shows that MEF-2C is strongly associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses demonstrated that MEF-2A independently predicts the progression-free interval (PFI) in NSCLC patients. Gene set enrichment analysis (GSEA) showed that MEF-2 family members are associated with immune cell receptor function and regulation of immunoglobulin complexes. The differentially expressed genes (DEGs) associated with MEF-2 family members were significantly enriched in the cAMP signaling pathway and gastric acid secretion. Gene ontology (GO) analysis revealed DEGs that play critical roles in the cytochrome-c oxidase activity, electron transfer activity, oxidoreduction-driven active transmembrane transporter activity; the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that they are mainly enriched in oxidative phosphorylation, thermogenesis, and diabetic cardiomyopathy. MEF-2A is a potential diagnostic, prognostic biomarker, and promising therapeutic target for NSCLC. Further studies are needed to verify and clarify the underlying mechanisms.

Keywords: Diagnostic and Prognosis; GO; GSEA; Immune Infiltration; KEGG analysis; MEF-2 family; Non-Small Cell Lung Cancer.

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Carcinoma, Non-Small-Cell Lung* / genetics
Carcinoma, Non-Small-Cell Lung* / metabolism
Carcinoma, Non-Small-Cell Lung* / pathology
Computational Biology* / methods
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms* / genetics
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology
MEF2 Transcription Factors* / genetics
MEF2 Transcription Factors* / metabolism
Prognosis

Substances

MEF2 Transcription Factors
Biomarkers, Tumor