AUTHOR=Ning Lvwen , Quan Chuntao , Wang Yue , Wu Zhijie , Yuan Peixiu , Xie Ni 

TITLE=scRNA-seq characterizing the heterogeneity of fibroblasts in breast cancer reveals a novel subtype SFRP4+ CAF that inhibits migration and predicts prognosis

JOURNAL=Frontiers in Oncology

VOLUME=Volume 14 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1348299

DOI=10.3389/fonc.2024.1348299

ISSN=2234-943X

ABSTRACT=Cancer-associated fibroblasts (CAFs) are a heterogeneous population of cells that influence the tumor microenvironment and the response to therapy in breast cancer (BC). Eight CAF subtypes were identified from single-cell RNA sequencing (scRNA-seq) in five tumor and six adjacent normal tissues. One of these subtypes, SFRP4+ CAFs, was novel and more prevalent in normal tissues. The existence of SFRP4+ CAFs were confirmed in two independent scRNA-seq datasets and a spatial transcriptomics dataset. We found that SFRP4+ CAFs inhibited BC cell migration and epithelial-mesenchymal transition (EMT) by secreting SFRP4 and modulating the WNT pathway. We also demonstrated that higher expression of SFRP4+ CAF markers was associated with better survival and treatment response in BC patients. Our study characterized the heterogeneity of CAFs in BC and showed a new SFRP4+ CAF subtype that suppresses BC migration, providing a potential biomarker for precision prognosis and therapy.