Fig. 8.

The coexpression of Twist1, Prrx1, and TNC is frequently found in cancer-associated fibroblasts and pathologic fibrosis. The clinical implications of the Twist1-Prrx1-TNC PFL in CAFs and fibrotic diseases. a, b We examined the coexpressions of all three genes by mIHC (scale bar indicates 100 μm). The bimodal distribution of the triple gene expression, all positive vs. all negative, a hallmark of a bistable system, was evident again in esophageal CAFs. These data are highly consistent with the computational prediction that the Twist1-Prrx1-TNC PFL functions may lead to irreversible and perpetual activation in pathologic conditions. We analyzed the expression profiles of these three genes in 306 esophageal cancer tissues. c The presence of CAFs that were positive for all three genes was strongly associated with the worse clinical outcomes. d Fibroblasts that were positive for all three genes were frequently observed in pathologic fibrosis, such as idiopathic pulmonary fibrosis, keloid disease, and desmoid tumors (aggressive fibromatosis). Scale bar indicates 100 μm