Fibroblasts in urothelial bladder cancer define stroma phenotypes that are associated with clinical outcome
Language English Country England, Great Britain Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
31937798
PubMed Central
PMC6959241
DOI
10.1038/s41598-019-55013-0
PII: 10.1038/s41598-019-55013-0
Knihovny.cz E-resources
- MeSH
- Actins metabolism MeSH
- Thy-1 Antigens metabolism MeSH
- CD8-Positive T-Lymphocytes cytology immunology metabolism MeSH
- Endopeptidases MeSH
- Phenotype MeSH
- Fibroblasts cytology metabolism MeSH
- Kaplan-Meier Estimate MeSH
- Humans MeSH
- Membrane Proteins metabolism MeSH
- Biomarkers, Tumor metabolism MeSH
- Urinary Bladder Neoplasms metabolism mortality pathology MeSH
- Prognosis MeSH
- Proportional Hazards Models MeSH
- Receptor, Platelet-Derived Growth Factor alpha metabolism MeSH
- Aged MeSH
- Serine Endopeptidases metabolism MeSH
- Cluster Analysis MeSH
- Gelatinases metabolism MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Actins MeSH
- Thy-1 Antigens MeSH
- Endopeptidases MeSH
- fibroblast activation protein alpha MeSH Browser
- Membrane Proteins MeSH
- Biomarkers, Tumor MeSH
- Receptor, Platelet-Derived Growth Factor alpha MeSH
- Serine Endopeptidases MeSH
- Gelatinases MeSH
Little attention was given to the interaction between tumor and stromal cells in urothelial bladder carcinoma (UBC). While recent studies point towards the existence of different fibroblast subsets, no comprehensive analyses linking different fibroblast markers to UBC patient survival have been performed so far. Through immunohistochemical analysis of five selected fibroblast markers, namely alpha smooth muscle actin (ASMA), CD90/Thy-1, fibroblast activation protein (FAP), platelet derived growth factor receptor-alpha and -beta (PDGFRa,-b), this study investigates their association with survival and histopathological characteristics in a cohort of 344 UBC patients, involving both, muscle-invasive and non-muscle-invasive cases. The data indicates that combinations of stromal markers are more suited to identify prognostic patient subgroups than single marker analysis. Refined stroma-marker-based patient stratification was achieved through cluster analysis and identified a FAP-dominant patient cluster as independent marker for shorter 5-year-survival (HR(95% CI)2.25(1.08-4.67), p = 0.030). Analyses of interactions between fibroblast and CD8a-status identified a potential minority of cases with CD90-defined stroma and high CD8a infiltration showing a good prognosis of more than 80% 5-year-survival. Presented analyses point towards the existence of different stroma-cell subgroups with distinct tumor-modulatory properties and motivate further studies aiming to better understand the molecular tumor-stroma crosstalk in UBC.
Charles University Faculty of Medicine in Pilsen Institut of Biology Plzen Czech Republic
Department of Immunology Genetics and Pathology Uppsala University Uppsala Sweden
Department of Oncology Pathology Karolinska Institutet Stockholm Sweden
Department of Surgical Sciences Uppsala University Uppsala Sweden
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