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Development of a Cancer-associated Fibroblast Signature for Evaluating Immunotherapy Response and Prognosis of Hepatocellular Carcinoma

  • 0Department of Hepatobiliary Surgery, Wuhan No.1 Hospital, Wuhan, 430022, China.
Current Medicinal Chemistry +

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July 18, 2024

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July 18, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Cancer-associated fibroblasts (CAFs) are crucial in hepatocellular carcinoma (HCC) development and treatment response. Targeting the CAF tumor microenvironment may improve personalized HCC treatment strategies.

Area Of Science

  • Oncology
  • Cancer Biology
  • Immunology

Background

  • Hepatocellular carcinoma (HCC) is often diagnosed at advanced stages, challenging effective treatment.
  • Key risk factors include alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and viral hepatitis (B and C).
  • Understanding the tumor microenvironment's role is critical for improving HCC patient outcomes.

Purpose Of The Study

  • To investigate the role of cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC) pathogenesis.
  • To develop a prognostic model based on CAF-related genes for HCC patients.
  • To explore the relationship between the CAF prognostic score (CAFPS) and drug sensitivity.

Main Methods

  • Analysis of HCC datasets from TCGA and GEO databases.
  • Quantification of tumor microenvironment (TME) components using the ESTIMATE algorithm.
  • Weighted gene co-expression network analysis (WGCNA) to identify CAF-associated gene modules.
  • Development of a CAF prognostic score (CAFPS) model using Cox regression.
  • Gene Ontology (GO) and KEGG pathway analyses.
  • Correlation analysis between CAFPS and drug sensitivity using GDSC.

Main Results

  • Significant differences in immune, stromal, CAF, and T-cell scores were observed across different HCC TNM stages.
  • WGCNA identified lightyellow and greenyellow modules strongly correlated with CAF scores.
  • Twelve prognostic CAF-related genes were identified, with high expression linked to lower survival.
  • The developed CAFPS model indicated that lower scores correlate with better patient survival.

Conclusions

  • Cancer-associated fibroblasts (CAFs) significantly influence HCC pathogenesis and treatment response.
  • Targeting the CAF-rich tumor microenvironment presents a potential therapeutic strategy for HCC.
  • The CAFPS model may aid in developing personalized treatment approaches for HCC patients.

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