MXD1 is a Potential Prognostic Biomarker and Correlated With Specific Molecular Change and Tumor Microenvironment Feature in Esophageal Squamous Cell Carcinoma.
Feng DuDezuo DongXiaodong ZhangJun JiaPublished in: Technology in cancer research & treatment (2022)
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.
Keyphrases
- prognostic factors
- poor prognosis
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- epithelial mesenchymal transition
- extracellular matrix
- stem cells
- genome wide
- cell proliferation
- peritoneal dialysis
- transcription factor
- gene expression
- magnetic resonance
- signaling pathway
- computed tomography
- protein protein
- climate change
- single molecule
- data analysis
- neural network
- nk cells