Positive Association of Matrix Proteins Alteration with TAZ and The Progression of High-Grade Bladder Cancer

Bladder cancer is the 9th leading cause of human urologic malignancy and the 13th cause of death worldwide. Increased collagen cross-linking, NIDOGEN1 expression and consequently stiffness of extracellular matrix (ECM) may be responsible for the mechanotransduction and regulation of transcriptional co-activator with PDZ-binding motif (TAZ) and transforming growth factor β1 (TGF-β1) signaling pathways, resulting in progression of tumorigenesis. The present study aimed to assess whether type 1 collagen expression is associated with TAZ nuclear localization.

In this case-control study, real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis were performed to evaluate the activation of the TAZ pathway in patients with bladder cancer (n=40) and healthy individuals (n=20). The ELISA method was also conducted to measure the serum concentrations of TGF-β1. Masson’s trichrome staining was carried out to histologically evaluate the density of type 1 collagen.

Our findings that the expression levels of COL1A1, COL1A2, NIDOGEN1, TAZ, and TGF-β1 genes were overexpressed in patients with bladder cancer, and their expression levels were positively associated with the grade of bladder cancer. The immunohistochemical analysis demonstrated that the nuclear localization of TAZ was markedly correlated with high-grade bladder cancer. We also found that TAZ nuclear localization was substantially higher in cancerous tissues as compared with normal bladder tissues. Masson's trichrome staining showed that the tissue density of type I collagen was considerably increased in patients with bladder cancer as compared with healthy subjects.

According to our findings, it seems the alterations in the expression of type I collagen and NIDOGEN1, as well as TAZ nuclear localization influence the progression of bladder cancer. The significance of TGF-β1 and TAZ expression in tumorigenesis and progression to high-grade bladder cancer was also highlighted. However, a possible relationship between TGF-β1 expression and the Hippo pathway needs further investigations.