Identification and Characterization of Metastasis-Initiating Cells in ESCC in a Multi-Timepoint Pulmonary Metastasis...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Metastasis remains a significant challenge in esophageal squamous cell carcinoma (ESCC) treatment.
• Understanding the early stages of metastasis is crucial for developing effective therapies.

Purpose of the Study:

• To identify and characterize metastasis-initiating cells (MICs) in ESCC.
• To discover molecular signatures associated with ESCC metastasis.
• To evaluate the predictive value of these signatures in clinical samples.

Main Methods:

• Single-cell RNA sequencing of lung metastatic ESCC cells in a mouse model.
• Differential gene expression analysis to identify metastasis-initiating signature genes (MIS).
• Functional assays to assess MIC capabilities.
• Multiplex immunohistochemistry (mIHC) on clinical ESCC samples.

Main Results:

• A subpopulation of ESCC cells (Cluster S) identified as MICs was found to colonize lung metastatic sites.
• Seven MIS, including CD44 and TACSTD2, were identified, with CD44high MICs showing enhanced survival, migration, invasion, stemness, and metastasis.
• Bioinformatics analysis suggested MICs may remodel the early metastatic microenvironment.
• Early metastasizing cells exhibited a quasi-epithelial-mesenchymal phenotype.
• Differential MIS expression scores (dMISs) in clinical samples predicted lymph node metastasis, overall survival, and carcinothrombosis risk.

Conclusions:

• MICs play a critical role in ESCC lung metastasis.
• The identified MIS, particularly CD44, are key drivers of ESCC metastatic potential.
• MIS expression levels can serve as predictive biomarkers for patient prognosis in ESCC.