Crotonylation-Related Prognostic Model of Esophageal Squamous Cell Carcinoma Based on Transcriptome Analysis and Single-Cell Sequencing Analysis.

BACKGROUND

Crotonylation is an emerging lysine acylation modification implicated in various diseases, yet its role in esophageal squamous cell cancer (ESCC) is unexplored. This study aimed to investigate the role of crotonylation-related genes (CRGs) in ESCC using bioinformatics approaches.

METHODS

We included three ESCC datasets and 24 CRGs. Differentially expressed genes (DEGs) from TCGA-ESCA were intersected with key module genes related to CRGs to identify candidate genes. Univariate and LASSO regression analyses were conducted to select prognostic genes, which were then used to construct risk models. Independent prognostic analysis and nomogram construction followed. Functional enrichment and immune infiltration analyses were performed using the prognostic genes. Single-cell analysis was conducted to assess cell communication and pseudotemporal dynamics in key cells.

RESULTS

Intersection of 1529 DEGs with 1,048 key module genes yielded 55 candidate genes. , and were identified as prognostic genes. These genes were used to classify ESCA patients into different risk groups and construct a nomogram. and FAM189A2 were enriched in neuroactive ligand-receptor interaction and ribosome terms. and FABP3 showed strong positive correlations with natural killer T (NKT) cells, while negatively correlated with gamma delta T (γδT) cells. Single-cell analysis identified mast cells and neutrophils as key cells, differentiating into seven and three states, respectively.

CONCLUSION

Four genes (, and ) were identified as prognostic crotonylation-related genes in ESCC, potentially involved in its pathogenesis. was negatively correlated with ESCC, while and were positively correlated.