gms | German Medical Science

Objective: YAP1 (yes-associated protein 1) and its homolog TAZ (transcriptional activator with PDZ-binding motif) are transcriptional co-activators of the hippo pathway which plays an important role in the regulation of tissue growth during organ growth and regeneration as well as in epithelial-mesenchymal transition (EMT). Alterations of YAP1- and TAZ-expression levels have been found in solid tumors like lung cancer, breast cancer and melanoma, as well as in primary brain tumors. We wanted to analyze the YAP1- and TAZ-expression in brain metastases of these tumors.

Methods: Samples of metastasis of melanoma (n=13), mamma carcinoma (n=20) and bronchial carcinoma (n=32) were obtained during neurosurgical resection. Levels of YAP1- and TAZ-expression were measured by qPCR and Western Blot. Statistical analysis was performed using GraphPad Prism 9.

Results: In qPCR, TAZ is significantly higher expressed in melanoma than in mamma carcinoma (p<0.0001) and in bronchial carcinoma (p=0.0009, Kruskal-Wallis test), expression is higher in bronchial than in mamma carcinoma (p=0.0009). For YAP1, expression is significantly higher in melanoma than in bronchial carcinoma (p<0.0001) and mamma carcinoma (p=0.0014). In Western Blotting, expression of TAZ is twice as high in melanoma than in bronchial carcinoma (p=0.028). Expression is lowest in mamma carcinoma (vs. melanoma p<0.0001; vs. bronchial p=0.0032). YAP1-expression is statistically significant higher in bronchial carcinoma than in melanoma (p=0.0003; Kruskal-Wallis test) and higher in mamma carcinoma than in melanoma (p=0.0541, Kruskal-Wallis test). Expression of YAP1 was higher in bronchial carcinoma than in mamma carcinoma, but the difference was not statistically significant (p=0.8207, Kruskal-Wallis test). While comparing TAZ-Expression of paired tumor samples in qPCR, level of expression was not different in primary than in relapsed samples (p=0.615). For YAP1-expression there was no statistical significance as well (p=0.8314).

Conclusion: Our research shows that melanoma has higher expression levels of YAP1/TAZ than mamma and lung carcinoma in qPCR and that the expression differs from primary to relapsed brain metastases. Targeting YAP1 or TAZ could be a promising approach to treat not only primary site carcinomas but also brain metastasis of relapsed tumor patients which have already been treated with various lines of therapy and have possibly developed resistances to them.