Identification of Molecular Subtypes Associated with PCD in Esophageal Squamous Cell Carcinoma and Analysis of Immune Microenvironment.

Background: Esophageal squamous cell carcinoma (ESCC) is a highly fatal malignancy with increasing incidence, and programmed cell death (PCD) plays an important role in homeostasis.

Aims: This study aimed to explore the ESCC of heterogeneity based on the PCD signatures for the diagnosis and treatment of patients.

Methods: The clinical information and RNA-seq data of patients with ESCC and the PCD-related genes set were used to identify PCD signatures.The "limma" package was used to identify the differentially expressed genes (DEGs). "Clusterprofiler" package was used for function enrichment analysis, and the "ConsensusClusterPlus" package was performed for consensus clustering. Finally, the "GSVA" package and the Cibersort algorithm were used for the immune infiltration analysis.

Results: We performed differential expression analysis between ESCC and normal samples and identified 1659 DEGs, of which 124 DEGs were PCD genes. Then, the patients were divided into cluster1 and cluster2 based on the expression of 124 PCD genes. There was a significant difference in immune infiltration between the two clusters. The patients in cluster 1 had a higher immune score and more CD56dim natural killer cells, monocytes, activated CD4 T cells, eosinophil, and activated B cells infiltration, while cluster2 had a higher stromal score, more immune regulation, and immune checkpoint genes expression.

Conclusion: We identified two clusters based on PCD gene expression and characterized their tumor microenvironment and immune checkpoint difference. Our findings may provide some new insight into the treatment of ESCC.