Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma
Yin Li, Fengkai Xu, Fanghua Chen, Yiwei Chen, Di Ge, Shu Zhang, Chunlai Lu
Abstract
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. METHODS: Expression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened. FINDINGS: fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy. INTERPRETATION: fibroblasts in TME, and identified potential drugs for clinical use. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.