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Single-Cell Transcriptomic Analysis Reveals an Aggressive Basal-Like Tumor Cell Subpopulation Associated With Poor
Changyi Liao1, Yuting Zhang2, Jing Yang3
1Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Journal of Gastroenterology and Hepatology
|February 24, 2025
Summary
Researchers identified a basal-like tumor cell subpopulation in intrahepatic cholangiocarcinoma (ICC). This aggressive subtype, driven by HGF-MET signaling, correlates with poor prognosis and presents a novel therapeutic target for ICC.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer with increasing incidence.
- High tumor heterogeneity in ICC limits current treatment efficacy.
Purpose of the Study:
- To dissect ICC tumor heterogeneity using single-cell RNA sequencing.
- To identify novel therapeutic targets for ICC.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) on 26 ICC tumor samples.
- Spatial transcriptomic sequencing on six ICC tumor sections.
- Validation using bulk RNA-seq, immunohistochemistry, and multiplex immunofluorescence staining.
Main Results:
- Identified a basal-like tumor cell subpopulation expressing KRT5, KRT6A, and KRT17.
- This subpopulation shows activated MET signaling and extracellular matrix organization, linked to invasion and poor prognosis.
- Inflammatory cancer-associated fibroblasts (iCAFs) secrete HGF, driving the basal-like phenotype via the HGF-MET axis.
Conclusions:
- An aggressive basal-like tumor cell subpopulation in ICC is associated with poor prognosis.
- The MET pathway promotes the aggressiveness of basal-like ICC cells.
- Targeting the MET pathway offers a potential therapeutic strategy for ICC.
