Fibroblasts activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses

Results: Inter-disease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and 4 signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analysis validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay (ELISA) revealed increased circulating levels of periostin in RDEB patients. Conclusions: Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving the abnormal ECM deposition and under-expression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. anti-Periostin (sc-398631), anti-Fibulin-1 (sc-25281), anti-TGase2 (sc-48387), and anti-GAPDH (sc-25778; Santa Cruz Biotechnology). Detection was performed using HRP-conjugated secondary antibodies and a chemiluminescent detection assay (SuperSignal West, Thermo Scientific). Three independent experiments were performed for each patient sample and controls.