Cancer-associated fibroblasts and the related Runt-related transcription factor 2 (RUNX2) promote bladder cancer progression.

Abstract

Bladder urothelial cancer (BLCA) has a high incidence worldwide. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are gradually recognized to play an important role in the occurrence and progression of cancer. However, the research on BLCA CAFs is still in its infancy, and the CAFs related genes are still unclear. We used the identified BLCA-specific CAFs gene signature in our previous work to calculate the CAFs infiltration score of the sample. Furthermore, we used data from multiple public databases to prove that CAFs high infiltration is associated with tumor progression and poor prognosis. In order to select the powerful genes in BLCA that are related to CAFs infiltration and affect prognosis, we chose transcription factors as the research object, and finally defined RUNX2 as the candidate gene for functional verification. In the immunohistochemical images, tissues with higher RUNX2 expression also had deeper staining of CAFs markers. We used public databases and collected specimens to prove that RUNX2 is overexpressed at the mRNA and protein levels in BLCA tissues. Through functional enrichment analysis, RUNX2 is mainly related to epithelialmesenchymal transition and extracellular matrix. Finally, we knocked down RUNX2 in vitro and observed a significant decrease in the metastasis and proliferation ability. In conclusion, high infiltration of CAFs is associated with tumor progression and poor prognosis in BLCA. RUNX2 is a transcription factor related to CAFs, which is overexpressed in bladder cancer and affects the prognosis. RUNX2 is a potential marker relating CAFs and therapy target in BLCA.