Abstract

Abstract Esophageal squamous cell carcinoma (ESCC) exhibits significant cellular heterogeneity, rendering it susceptible to developing radioresistance and recurring tumors. Single-cell RNA sequencing (scRNA-seq) is an advanced technique that allows for the exploration of distinct gene expression profiles in individual cells. To investigate cellular heterogeneity in ESCC, scRNA-seq analysis was performed on tumor tissues from ten ESCC patients, as well as adjacent non-malignant esophageal tissues. The cellular composition revealed 19 distinct cell clusters, further categorized into seven cell populations: 69.31% Fibroblast, 15.36% T cell, 5.30% Monocytes, 5.26% Endothelial cells, 2.68% plasma cell, 1.91% Epithelial cells, and 0.18% ambiguous. Notably, Fibroblast and Endothelial cells were more prevalent in non-malignant tissues, while the remaining cell types were enriched in tumor tissues. Differential gene expression analysis identified 49 genes with higher expression in tumor cells and 37 genes with lower expression. Gene Set Enrichment Analysis (GSEA) revealed the top three most relevant GO Biological Processes pathways: positive regulation of immune response, regulation of T cell activation, and positive regulation of cell migration. Furthermore, in post-treatment follow-up, four patients were observed to develop metastasis within one year. Comparative analysis between metastatic and non-metastatic patients unveiled 9 Differentially Expressed Genes (DEGs), including KRT6A and AKR1B10, which exhibited specific expression in Epithelial cells and were highly expressed in tumor tissues. Additionally, IGLC2, IGHG4, and IGHG1 demonstrated specific expression in plasma cells, with elevated expression in tumor tissues. These findings suggest that KRT6A, AKR1B10, IGLC2, IGHG4, and IGHG1 may serve as potential biomarkers for predicting post-chemotherapy metastasis in ESCC patients. Citation Format: Tzu-Hung Hsiao, Chih-Hung Lin, Ting-Shuan Wu, Li-Wen Lee, Chung-Ping Hsu. Characterizing Cellular Heterogeneity and Identifying Potential Biomarkers in Esophageal Squamous Cell Carcinoma (ESCC) Using Single-Cell RNA Sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5674.

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