Naslov
DVL1, TWIST1, SNAIL and SLUG as nuclear markers of meningioma progression
(DVL1, TWIST1, SNAIL and SLUG as nuclear markers of meningioma progression)

Autori
Bukovac, Anja ; Dragičević, Katarina ; Kafka, Anja ; Šlaus, Nika ; Njirić, Niko ; Marković, Leon ; Pećina-Šlaus, Nives

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
EACR 2022 Congress online abstracts / - , 2022

Skup
28th Congress of the European association for cancer research

Mjesto i datum
Sevilla, Španjolska, 20.06.2022. - 23.06.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
DVL1 ; TWIST1 ; SNAIL and SLUG ; meningioma

Sažetak
Introduction: Meningiomas are mostly benign tumors, but in small portion can develop malignant characteristics through progression to atypical and anaplastic grades. Those grades are more difficult to treat with classic therapies, therefore there is a continuing quest for molecular candidates for targeted meningioma treatments. Our focus was on discovering if Wnt signaling pathway and epithelial–mesenchymal transition (EMT), which are known to be involved in meningioma progression, can offer new molecular candidates for meningioma prognosis. Material and method: We performed DAB-labelled immunohistochemical reactions on formalin-fixed paraffin-embedded meningioma sections with antibodies that detect active beta-catenin, DVL1, E-cadherin, N-cadherin, TWIST1, SNAIL&SLUG. Involvement of genetic changes in protein expression was tested using standard Sanger sequencing which gave us insight into exon 3 mutation hotspot of CTNNB1 (beta-catenin) and PDZ domain of DVL1. Results and discussion: We discovered that DVL1, a central mediator of Wnt signaling pathway, as well as EMT transcription factors TWIST1, SNAIL and SLUG could be a good candidates as nuclear markers of meningioma progression. The most pronounced result showed that the nuclear expression of DVL1 was significantly correlated with a higher expression of active β-catenin (p = 0.029) and a higher meningioma grade (p = 0.030). This was also true for SNAIL and SLUG expression, which was significantly associated with higher meningioma grades (p = 0.001). TWIST1 didn’t show statistical correlation with higher grades but was pronounced in most samples and its increased expression followed an increase of SNAIL and SLUG expression (p = 0.033). The high protein expression of EMT transcription factors could be the reason for observed low levels of E-cadherin in our samples. Interestingly, beta-catenin, although active, was found only in cytoplasm and was absent from nuclei. Genetic analysis showed that exon 3 of CTNNB1 was mutated in 22.2% of samples and was absent in anaplastic samples, suggesting to be driving mutations of meningioma and not related to progression. On the other hand, the PDZ domain of DVL1 was severely mutated and usually led to lower expression of DVL1. Conclusion: Our study confirmed the role of key actors of conserved Wnt signaling pathway and EMT in intracranial meningioma progression. Furthermore, it suggests new molecular candidates for diagnostics and the treatment of meningioma patients.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti, Temeljne medicinske znanosti

POVEZANOST RADA