Construction of a multigenic diagnostic, prognostic, and immune infiltration model with methylation-associated regulators in esophageal squamous cell carcinoma.

BACKGROUND

Methylation-related regulators may be involved in the prognostic prediction of esophageal squamous cell carcinoma (ESCC). Our study aimed to apply bioinformatics to screen methylation-related regulators for the construction of a prognostic model for patients with ESCC and to assess their diagnostic value and correlation with immune infiltration.

METHODS

Prognosis-related genes were identified from The Cancer Genome Atlas (TCGA) database. Methylation-associated genes were filtered using the GeneCards database. We used the least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression to identify the prognostic indicators. We applied the single-sample gene set enrichment analysis (ssGSEA) to clarify the relationship between prognostic indicators and immune infiltration in patients with ESCC (n=82).

RESULTS

We constructed a prognostic model using methylation-related regulators homocysteine-inducible ER protein with ubiquitin-like domain 1 (), trans-2,3-enoyl-CoA reductase (), melanoma antigen gene A11 (), and NOP2/Sun RNA methyltransferase 6 () to evaluate the prognosis of patients with ESCC. A higher prognostic risk score was associated with shorter overall survival (OS) in patients with ESCC [hazard ratio (HR) =5.77, 95% confidence interval (CI): 2.13-15.58; P<0.001]. Time-dependent area under the curve (AUC) analysis revealed that , and had high prognostic predictive value at different time points. Furthermore, we found that the combined diagnostic model based on , and had excellent diagnostic efficacy for ESCC (AUC =0.911; 95% CI: 0.888-0.935). Finally, the ssGSEA algorithm showed that was significantly positively correlated with immune infiltration at both the cellular and genetic levels, while showed a significant negative correlation with immune infiltration levels.

CONCLUSIONS

Our prognostic model, built with the methylation-related regulators , and , could effectively predict prognosis in patients with ESCC, enhance diagnostic efficacy, and reflect immune cell infiltration in their microenvironment. Our findings are hypothesis generating and larger confirmatory studies are needed to validate our results.