Article
Higher YAP1 levels result in shorter survival of low grade astrocytoma patients
Hohe YAP1 Level resultieren in kürzerem Überleben in LGG Patienten
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Published: | May 25, 2022 |
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Objective: YAP1 (yes-associated protein 1) and its homologue TAZ (transcriptional activator with PDZ-binding motif) are transcriptional co-activators of the hippo pathway. This pathway plays an important role in the regulation of tissue growth during organ growth and regeneration. When the hippo-pathway is inhibited, YAP/TAZ accumulate in the nucleus and bind to transcription factors whose target genes code for proteins of cell proliferation, differentiation and epithelial-mesenchymal transition (EMT). Alterations of YAP/TAZ-expression-levels have been found in different solid tumors such as lung, breast, hepatocellular and ovarian cancer. Knockdown of TAZ in GBM-cell-lines results in less invasion and migration, while an upregulation enhances these drivers of tumorigenesis. YAP1-overexpression results in more invasion and migration in GBM-cells and is related to poorer prognosis as well. In this study we wanted to examine the influence of YAP1- and TAZ-expression on survival in patients with astrocytoma and oligodendroglioma by measuring mRNA expression rates in vivo.
Methods: Samples of primary (n=29) and recurrent (n=31) low grade glioma were obtained during neurosurgical resection. Histological diagnosis was made by an independent neuropathologist using the WHO Classification of 2007. Levels of YAP1 and TAZ-expression were measured by qPCR. Statistical analysis was performed using GraphPad Prism 9.
Results: In YAP1, the expression in astrocytomas was twice as high as in oligodendrogliomas with a mean of 1.578 vs. 0.7003 (p=0.0177, Unpaired t-test). In oligodendrogliomas, relapsed tumors showed significantly higher expression-levels of TAZ than primary tumors (p=0.0305) with means of 0.4464 and 0.1667. In astrocytomas, patients with low TAZ-expression showed a significant longer OS than patients with high TAZ-expression (median survival 149 vs. 84 months, p=0.0422). The OS of patients with low YAP1-expression was also longer than that of patients with high YAP1-expression (median survival 161 vs. 86 months, p=0.0248). In oligodendrogliomas, there were no significant differences in OS in patients with low vs. high TAZ-expression (median survival 154 vs. 186 months, p=0.3709) and with low vs. high YAP1-expression (median survival 131 vs. 191 months, p=0.2497).
Conclusion: YAP1 plays an important role in LGG and not only in HGG and should be considered as molecular marker and target in therapy.