Analysis of the crosstalk between EMT-related gene and Tumor-infiltrating immune cell in Esophageal Squamous Cell Carcinoma

Abstract Background: Esophageal squamous cell carcinoma (ESCC) has the leading rate of metastasis and mortality, so effectively suppressing cancer progression and prolonging the long-term prognosis has always been a proactive and challenging task. Methods: This study aimed to identify the promising biomarkers related to epithelial-mesenchymal transition (EMT) and attempted to elucidate the potential role of the crosstalk between the EMT process and tumor infiltrating immune cell in the tumorigenesis and progression of ESCC. Based on the combined analysis of mouse esophageal cancer models and ESCC patients, we identified 5 novel EMT biomarkers (PLAUR, TIMP1, LAMC2, COL7A1 and IGFBP3), which are significantly up-regulated during ESCC tumorigenesis. Based on the expression of these 5 genes, ESCC patients were clustered into three subgroups (cluster 1, cluster 2 and cluster 3). Results: Notably, compared to cluster 2, patients in cluster 3 had higher expression of EMT-related genes (ZEB1, Vimentin, Snail, and Slug), higher infiltration of myeloid dendritic cells and M2 macrophages, and lower infiltration of T regulatory cells (Tregs). Moreover, we also demonstrated that ESCC patients with high infiltration of Tregs had lower expression of Vimentin and Snail, while patients with high infiltration of M2 macrophage had higher expression of ZEB1, Vimentin and Snail. Finally, through multi-cohort correlation analysis and verification, we identified 4 core biomarker-related ceRNA networks (LAMC2-MIR193BHG axis, LAMC2-MIR4435-2HG axis, LAMC2-PLAUR axis and PLAUR-LINC00707 axis). Conclusions: In summary, we identified and initially validated 5 EMT biomarkers, and investigated the interaction of EMT process and tumor infiltrating immune cell in ESCC.