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Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome
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Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome
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Journal Article
Cancer-associated fibroblasts expressing fibroblast activation protein and podoplanin in non-small cell lung cancer predict poor clinical outcome
2024
Overview
Background
Cancer-associated fibroblasts (CAFs) are a dominant cell type in the stroma of non-small cell lung cancer (NSCLC). Fibroblast heterogeneity reflects subpopulations of CAFs, which can influence prognosis and treatment efficacy. We describe the subtypes of CAFs in NSCLC.
Methods
Primary human NSCLC resections were assessed by flow cytometry and multiplex immunofluorescence for markers of fibroblast activation which allowed identification of CAF subsets. Survival data were analysed for our NSCLC cohort consisting of 163 patients to understand prognostic significance of CAF subsets.
Results
We identified five CAF populations, termed CAF S1-S5. CAF-S5 represents a previously undescribed population, and express FAP and PDPN but lack the myofibroblast marker αSMA, whereas CAF-S1 populations express all three. CAF-S5 are spatially further from tumour regions then CAF-S1 and scRNA data demonstrate an inflammatory phenotype. The presence of CAF-S1 or CAF-S5 is correlated to worse survival outcome in NSCLC, despite curative resection, highlighting the prognostic importance of CAF subtypes in NSCLC. TCGA data suggest the predominance of CAF-S5 has a poor prognosis across several cancer types.
Conclusion
This study describes the fibroblast heterogeneity in NSCLC and the prognostic importance of the novel CAF-S5 subset where its presence correlates to worse survival outcome.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Aged
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Biomedical and Life Sciences
/ Cancer-Associated Fibroblasts - metabolism
/ Cancer-Associated Fibroblasts - pathology
/ Carcinoma, Non-Small-Cell Lung - genetics
/ Carcinoma, Non-Small-Cell Lung - metabolism
/ Carcinoma, Non-Small-Cell Lung - mortality
/ Carcinoma, Non-Small-Cell Lung - pathology
/ Female
/ Fibroblast activation protein
/ Humans
/ Male
/ Membrane Glycoproteins - genetics
/ Membrane Glycoproteins - metabolism
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Non-small cell lung carcinoma
/ Oncology
/ Serine Endopeptidases - genetics
/ Serine Endopeptidases - metabolism
/ Stroma
