The potential of MCM8 as a biomarker in esophageal carcinoma: a comprehensive analysis integrating m6a methylation and angiogenesis.

Background: Effective biomarkers for esophageal carcinoma (ESCA) are currently lacking. Here, we examined the role of minichromosome maintenance complex component 8 (MCM8) as a diagnostic and prognostic marker in ESCA and its association with m6a methylation and angiogenesis, and constructed a competing endogenous RNA (ceRNA) network.

Methods: Clinical data and gene expression profiles were obtained from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Differential gene expression analysis was performed using DESeq2 and limma packages. The prognostic significance of MCM8 expression regarding overall survival (OS) was examined using the Cox proportional hazards model. Receiver Operating Characteristic (ROC) analysis was used to assess the diagnostic potential of MCM8. MCM8 expression in ESCA tissues was evaluated by immunohistochemical staining on a tissue microarray. Pearson correlation analysis identified co-expressed genes, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The GEPIA online tool was used to examine the relationship between MCM8 and m6a methylation as well as angiogenesis-related genes. MicroRNA and long noncoding RNA predictions were made using miRWalk, MicroT-CDS, ENCORI, and miRNet tools to construct the ceRNA network.

Results: MCM8 was significantly overexpressed in tumor tissues and showed high diagnostic accuracy in the ROC analysis with an area under the curve of 0.920. Kaplan-Meier survival analysis revealed that high MCM8 expression correlated with poorer OS and disease-specific survival. Pearson correlation analysis identified a significant correlation between MCM8 and several m6a methylation-related genes such as HNRNPA2B1 and YTHDF1, as well as PTK2, an angiogenesis-related gene. A ceRNA network including MCM8, PURPL/hsa-miR- 135a- 5p/MCM8 was successfully predicted and constructed.

Conclusions: MCM8 is a promising biomarker in ESCA and it is associated with m6a methylation and angiogenesis, showing potential as a therapeutic target. The ceRNA network provided insight into the pathogenesis of ESCA.