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Integration of Multi-Scale Profiling and Machine Learning Reveals the Prognostic Role of Extracellular Matrix-Related Cancer-Associated Fibroblasts in Lung Adenocarcinoma

  • 0Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
International Journal of Medical Sciences +

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July 14, 2025

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July 14, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Extracellular matrix cancer-associated fibroblasts (eCAFs) and SPP1+ macrophages drive lung adenocarcinoma (LUAD) progression. Targeting their interaction may offer new therapeutic strategies for LUAD patients.

Area Of Science

  • Oncology
  • Immunology
  • Genomics

Background

  • Lung adenocarcinoma (LUAD) is a major cause of cancer death, requiring new therapeutic targets.
  • The tumor microenvironment, including cancer-associated fibroblasts (CAFs) and macrophages, significantly influences LUAD progression.

Purpose Of The Study

  • To investigate the role of extracellular matrix cancer-associated fibroblasts (eCAFs) and SPP1+ macrophages in LUAD.
  • To identify potential therapeutic targets and prognostic markers in LUAD based on stromal-immune interactions.

Main Methods

  • Single-cell RNA sequencing of 15 LUAD tumors.
  • Integration of multi-cohort transcriptomic data (TCGA, GSE31210, GSE72094).
  • Pseudotime trajectory and cell-cell communication analyses, machine learning for prognostic model development.

Main Results

  • eCAFs were identified as a dominant CAF subtype in advanced LUAD, associated with poor survival.
  • SPP1+ macrophages were more abundant in advanced tumors and linked to adverse prognosis.
  • eCAFs interact with SPP1+ macrophages via COL1A1-CD44 and COL1A2-CD44, potentially creating immune-excluded microenvironments.
  • A 28-gene prognostic signature derived from eCAFs effectively stratified LUAD patients into risk groups.

Conclusions

  • eCAFs are key drivers of LUAD progression, and their crosstalk with SPP1+ macrophages is a potential therapeutic target.
  • The eCAFs-related prognostic signature provides clinical utility for LUAD risk stratification.
  • ECM remodeling is a critical pathway in LUAD evolution, highlighting stromal-immune interactions.

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