MXD1 is a Potential Prognostic Biomarker and Correlated With Specific Molecular Change and Tumor Microenvironment Feature in Esophageal Squamous Cell Carcinoma.

Background

Identification of novel biomarkers is crucial for the diagnosis and treatment of esophageal squamous cell carcinoma (ESCC). This study aimed to reveal the clinical significance and molecular characteristics of MYC-associated factor X dimerization protein 1 (MXD1) in ESCC. Patients and methods: We collected 3 ESCC cohorts to investigate the effect of MXD1 on clinical outcomes. In addition, we compared and analyzed the possible transcription changes between MXD1-low and MXD1-high ESCC patients using bioinformatics. Moreover, immunohistochemical analysis was conducted to confirm the potential impact of MXD1 on the prognosis and tumor immune microenvironment (TIME).

Results

MXD1 messenger RNA (mRNA) expression was significantly lower in tumors than in normal tissues. Low expression of MXD1 in ESCC was associated with a more aggressive tumor stage and worse prognosis at both the mRNA and protein levels. Moreover, MXD1-low ESCC showed upregulation of epithelial-mesenchymal transition and extracellular matrix-related gene sets, and significantly higher NFE2L2 and KIAA1324L mutation frequencies. In contrast, MXD1-high ESCC showed upregulation of tumor differentiation and immune-related gene sets. Furthermore, the CIBERSORT approach showed that high expression of MXD1 was associated with a higher proportion of neutrophils but a lower proportion of M2 macrophages. At the protein level, MXD1 expression was positively correlated with programmed cell death 1 ligand 1 (PDL1) and CD8 expression. In silico analysis predicted that MXD1-high ESCC was more likely to benefit from immunotherapy.

Conclusion

This study suggests that MXD1 is a crucial prognostic factor in ESCC patients and is closely associated with specific transcriptional changes and TIME features.