MEF2A, MEF2C, and MEF2D as potential biomarkers of pancreatic cancer?

The myocyte enhancer factor-2 (MEF2) family genes were involved in the carcinogenesis and prognosis of multiple human tumors. The impact of MEF2s on the occurrences, progression, and clinical outcome of pancreatic cancer (PAAD) remains unknown.

This study used the CCLE, HPA, EMBL-EBI, and GEPIA2 databases to study MEF2s expression in PAAD patients. We also investigated the relationship between MEF2s expression and methylation through the DiseaseMeth database, and used MEXPRESS to verify the association. Then we utilized the Kaplan-Meier Plotter and GEPIA2 databases to evaluate the prognostic value of MEF2s in PAAD. The cBioPortal database was used to explore the alteration features of MEF2s in PAAD. We then investigated the association between MEF2s expression, immune cells infiltration, and immune infiltration markers using the TIMER database. Finally, Metascape, STRING, and Cytoscape tools were used for functional enrichment analysis.

MEF2A, MEF2C, and MEF2D were found to be highly expressed in PAAD patients' tissues compared to normal tissues, whereas MEF2B expression did not show significant differential expression. In addition, the protein expression of MEF2A, MEF2C, and MEF2D was higher in PAAD tissues. Negative correlations were observed between the expression level of MEF2A, MEF2C, and MEF2D and the methylation levels in multiple sites. High expression of MEF2A was related to poor overall survival (p = 0.0071) and relapse-free survival (RFS) (p = 0.0089) of PAAD. High expression of MEF2C was associated with worse RFS of PAAD (p = 0.043). MEF2A was a Truncating mutation, and it was shown that the "G27Wfs*8" mutation point was distributed in the SRF-TF domain. Both MEF2C and MEF2D were a Missense mutation. MEF2A, MEF2C, and MEF2D expression was positively corresponded with five immune cells infiltration (CD8 + T cells, B-cells, neutrophils, macrophages, and dendritic cells), especially for CD8 + T cells and macrophages. Among the 20 pathways, hsa05140 (Leishmania infection), hsa04022 (cGMP-PKG signaling pathway), hsa05145 (Toxoplasmosis), hsa04371 (Apelin signaling pathway), and hsa04064 (NF-kappa B signaling pathway), were closely connected with the occurrence and development of PAAD.

Our results indicated that the overexpression of MEF2A, MEF2C, and MEF2D in patients with PAAD. MEF2A could be used as a prognostic biomarker for PAAD, MEF2C might be a potential oncogene for PAAD, and MEF2D had potential biological significance.