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Extracellular cancer‑associated fibroblasts: A novel subgroup in the cervical cancer microenvironment that exhibits

Yuehan Wang1, Mingxia Xu1, Yeli Yao2

  • 1Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.

Oncology Letters
|March 7, 2024
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Summary

Researchers identified distinct cancer-associated fibroblast (CAF) subtypes in cervical cancer. A novel risk signature based on extracellular CAFs (ecCAFs) accurately predicts patient survival and may offer new therapeutic targets.

Keywords:
cancer-associated fibroblastcervical cancerprognosissingle-cell RNA sequencingtherapeutic responsetumor microenvironment

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Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • Tumor invasion and metastasis are primary drivers of poor outcomes in cervical cancer.
  • Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression and metastasis, representing potential therapeutic targets.
  • Understanding CAF heterogeneity within the tumor microenvironment is essential for developing effective treatments.

Purpose of the Study:

  • To investigate the heterogeneity of CAFs in the cervical cancer microenvironment using single-cell RNA sequencing.
  • To identify distinct CAF subtypes and their respective roles in tumor progression.
  • To develop a prognostic risk signature based on CAF characteristics for cervical cancer patients.

Main Methods:

  • Single-cell RNA sequencing was employed to analyze CAFs from cervical cancer samples.
  • CAF subtypes, myofibroblastic CAFs (myCAFs) and extracellular CAFs (ecCAFs), were identified and characterized.
  • Enrichment analysis, Cox regression, and least absolute shrinkage and selection operator (LASSO) analyses were used to build a CAF-associated risk signature.
  • The Cancer Genome Atlas (TCGA) and Gene Ontology databases were utilized for gene expression data.

Main Results:

  • Cervical cancer-associated fibroblasts were classified into myCAFs and ecCAFs.
  • Extracellular CAFs (ecCAFs) exhibited stronger pro-tumorigenic effects compared to myCAFs.
  • A robust CAF-associated risk signature was developed, demonstrating stable prognostic capability in training and validation cohorts.
  • The risk signature correlated with the tumor immune microenvironment and therapeutic responses, and showed predictive value for other HPV-associated cancers.

Conclusions:

  • Cervical cancer exhibits CAF heterogeneity, with ecCAFs identified as a pro-tumorigenic subgroup.
  • A novel prognostic signature based on ecCAF hub genes can predict survival rates in cervical cancer patients.
  • This ecCAF subgroup represents a potential therapeutic target for cervical cancer treatment.