Abstract 6270: Integrating spatial transcriptomics and single-cell RNA-seq reveal the tumorigenesis and heterogeneity of esophageal squamous cell carcinoma

Abstract

Abstract Background: Esophageal cancer is the sixth leading cause of cancer death globally and esophageal squamous cell carcinoma (ESCC) is the major histological type in China. The heterogeneity of ESCC resulted in poor therapeutic effect and tumor recurrence. To investigate the heterogeneity of ESCC at the single-cell level and the oncogenic evolution, we performed single-cell RNA-seq and spatial transcrtiptomics analysis in ESCC samples from different patients and position. Methods: We performed single-cell RNA-seq of tumor, adjacent normal tissue and the junction of cancer and normal tissues from 4 ESCC patients. We also performed spatial transcriptomics of paired cancer, normal and junction of ESCC patients. Unsupervised clustering was performed to find different cell clusters of ESCC and marker genes of different clusters were determined. Inferred copy number variation was performed to identify malignant cells and pseudotime analysis to investigate the development of different cell clusters. Combined analysis of single-cell and spatial data was performed to reveal the spatial characteristics of different cell types. Results: We successfully determined different cell types including epithelial cells, immune cells, fibroblasts, myeloid cells and so on. And we also reclustered epithelial, myeloid and T/NK cells to investigate different subtypes and their marker genes. We also distinguished malignant cells from heterogeneous cellular populations using inferred copy number variation analysis. Pseudotime analysis revealed the evolution of different cell types of ESCC. We identified key signatures associated with oncogenic evolution of ESCC and the spatial characteristics of key cell clusters. Conclusion: These findings reveal the heterogenesis of ESCC and key signatures in ESCC tumorigenesis. Keywords: ESCC, single cell sequencing, spatial transcriptomics, heterogeneity, tumorigenesis Citation Format: Xiaoyang Yin, Baosheng Li. Integrating spatial transcriptomics and single-cell RNA-seq reveal the tumorigenesis and heterogeneity of esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6270.