FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).

Abstract

While preclinical studies consistently implicate FGFR‑signalling in breast cancer (BC) progression, clinical evidence fails to support these findings. It may be that the clinical significance of FGFR ought to be analysed in the context of the stroma, activating or repressing its function. The present review aimed to provide such a context by summarizing the existing data on the prognostic and/or predictive value of selected cancer‑associated fibroblasts (CAFs)‑related factors, that either directly or indirectly may affect FGFR‑signalling. PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Medline (https://www.nlm.nih.gov/medline/medline_home.html) databases were searched for the relevant literature related to the prognostic and/or predictive significance of: CAFs phenotypic markers (αSMA, S100A4/FSP‑1, PDGFR, PDPN and FAP), CAFs‑derived cognate FGFR ligands (FGF2, FGF5 and FGF17) or inducers of CAFs' paracrine activity (TGF‑β1, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF) both expressed in the tumour and circulating in the blood. A total of 68 articles were selected and thoroughly analysed. The findings consistently identified upregulation of αSMA, S100A4/FSP‑1, PDGFR, PDPN, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF as poor prognostic markers in BC, while evaluation of the prognostic value of the remaining markers varied between the studies. The data confirm an association of CAFs‑specific features with BC prognosis, suggesting that both quantitative and qualitative profiling of the stroma might be required for an assessment of the true FGFR's clinical value.