Introduction:
This study aimed to explore the potential genetic and epigenetic mechanisms associated with IDO1 mRNA dysregulation in esophageal cancer (ESCA).

Material and methods:
Data from The Cancer Genome Atlas (TCGA)-ESCA and the Genotype-Tissue Expression (GTEx) project were obtained for analysis. Subgroup analysis was performed in esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (ESAD).

Results:
IDO1 mRNA expression was significantly upregulated in ESAD and ESCC tissues compared to normal esophagus. Although gene-level copy number alterations were common in both ESAD and ESCC, they were not associated with IDO1 dysregulation. Among 3 CpG sites (cg10262052 and cg08465774 in promoter and cg24188163 in gene body) in the IDO1 gene locus examined, only cg10262052 was hypomethylated in cancerous tissues compared to normal tissues in ESAD. All 3 sites showed significantly different methylation in ESCC than in normal tissues, among which cg10262052 and cg08465774 were hypomethylated, while cg24188163 was hypomethylated. Correlation analysis confirmed negative correlations between cg10262052/cg08465774 methylation and IDO1 expression, while cg24188163 methylation was positively correlated with IDO1 expression (Pearson’s r = 0.45) in ESCC patients. Genomic study confirmed that cg24188163 is in the flanking region of an intragenic promoter of IDO1. IDO1 expression had an independent prognostic value in terms of overall survival (OS) in ESCC patients (HR = 1.183, 95% CI: 1.025–1.367, p = 0.022), but was not a risk factor of unfavorable OS in ESAD patients.

Conclusions:
IDO1 mRNA upregulation was associated with both promoter hypomethylation and gene body hypermethylation in ESCC. Its expression has a specific prognostic value in terms of OS in ESCC, but not in ESAD patients.