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  3. Single-cell transcriptomic analysis reveals the landscape of epithelial-mesenchymal transition molecular heterogeneity in esophageal squamous cell carcinoma

Single-cell transcriptomic analysis reveals the landscape of epithelial-mesenchymal transition molecular heterogeneity in esophageal squamous cell carcinoma

  • Cancer Lett. 2024 Feb 10:587:216723. doi: 10.1016/j.canlet.2024.216723.
Dianhao Guo 1,  Kaiwen Sheng 2,  Qi Zhang 3,  Pin Li 4,  Haoqiang Sun 5,  Yongjie Wang 6,  Xinxing Lyu 7,  Yang Jia 8,  Caifan Wang 9,  Jing Wu 10,  Xiaohang Zhang 11,  Dandan Wang 12,  Yawen Sun 13,  Shuhong Huang 14,  Jinming Yu 15,  Jingze Zhang 16
Affiliations

Affiliations

  • 1 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 2 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 3 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 4 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 5 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 6 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 7 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 8 Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 9 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 10 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 11 Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau. Electronic address: [email protected].
  • 12 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 13 Department of Clinical Epidemiology and Biostatistics, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 14 School of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
  • 15 Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China; Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: [email protected].
  • 16 Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, China. Electronic address: [email protected].
PMID: 38342234 DOI: 10.1016/j.canlet.2024.216723
Abstract

Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly lethal malignant disease. The epithelial-mesenchymal transition (EMT) is crucial in promoting ESCC development. However, the molecular heterogeneity of ESCC and the potential inhibitory strategies targeting EMT remain poorly understood. In this study, we analyzed high-resolution single-cell transcriptome data encompassing 209,231 ESCC cells from 39 tumor samples and 16 adjacent samples obtained from 44 individuals. We identified distinct cell populations exhibiting heterogeneous EMT characteristics and identified 87 EMT-associated molecules. The expression profiles of these EMT-associated molecules showed heterogeneity across different stages of ESCC progression. Moreover, we observed that EMT primarily occurred in early-stage tumors, before lymph node metastasis, and significantly promoted the rapid deterioration of ESCC. Notably, we identified SERPINH1 as a potential novel marker for ESCC EMT. By classifying ESCC patients based on EMT gene sets, we found that those with high EMT exhibited poorer prognosis. Furthermore, we predicted and experimentally validated drugs targeting ESCC EMT, including dactolisib, docetaxel, and nutlin, which demonstrated efficacy in inhibiting EMT and metastasis in ESCC. Through the integration of scRNA-seq, RNA-seq, and TCGA data with experimental validation, our comprehensive analysis elucidated the landscape of EMT during the entire course of ESCC development and metastasis. These findings provide valuable insights and a reference for refining ESCC clinical treatment strategies.

Keywords

Cancer-associated fibroblasts; Epithelial-mesenchymal transition; Molecular heterogeneity; Single-cell transcriptomic analysis; Targeted drugs.

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