Molecular classification of esophageal squamous cell carcinoma based on immunogenic cell death related damage-associated molecular pattern gene signature

Abstract

Abstract Background Esophageal squamous cell carcinoma (ESCC) has a prognosis. Understanding the molecular heterogeneity in ESCC is essential for designing novel immunotherapies to improve prognosis. Immunogenic cell death (ICD) releases damage-associated molecular patterns (DAMP) that may help to the adaptive immune response of cancers, thereby may guiding immunotherapy for patients with ESCC. This study was aimed to identify DAMPs related molecular subtypes in ESCC. Methods RNA-seq data of TCGA-ESCC (n = 79) were downloaded, and the samples were randomly classified into training and validation sets. DAMPs related gene set was extracted from the literature. Differential expression analysis was performed using DESeq2. Tumor samples were performed consensus clustering analysis to identify the subtypes of ESCC. Then immune microenvironment, genome, drug sensitivity, and function between subtypes were analyzed. Results Total 32 DAMP related differential expressed genes were identified and two subtypes were obtained based on these genes. The prognosis of Cluster1 was significantly better than that of Cluster2. The up-regulated genes in Cluster1 were involved in tumor-related functions and pathways, while in Cluster2 were associated with immunity and inflammation. Cluster1 had a significantly higher copy number variation (CNV) rate compared to Cluster2. There were higher immune cell infiltration proportion, immune score, immune checkpoint genes and MHC genes expression in Cluster2 compared with in Cluster1. Conclusion This study for the first time identified the molecular subtypes of ESCC based on ICD-associated DAMP genes. Findings of this study may facilitate the development of individualized tumor immunotherapy.