Yüksek dereceli gliomlarda invazyon belirteçlerinin ekspresyonunun ve klinik öneminin araştırılması
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Tarih
2022
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Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Gliomalar primer beyin tümörleri içerisinde en sık rastlanan histolojik tiptir. Erken dönemde tekrarlayan nüksler ile invaziv seyreden bu tümörlerin ortalama sağkalım süresi 1-2 yıldır (2). İçinde genetik mutasyonlar ve moleküler anormallikler barındıran YDG’lerde görülen erken nüks ve kısa sağkalım tümörün invazyon ve neoanjiyogenez yolaklarında rol oynayan moleküllerde çeşitli mutasyonlar ve ekspresyon değişikliklerine bağlanmaktadır (3). Moleküler ve genetik olarak heterojen bir grup olan bu tümörlerde değişik invazyon ve anjiyogenez yolakları ile ilgili birçok çalışma yapılmakla birlikte bu çalışmaların tamamına yakını hücre kültürlerinde ya da deneysel hayvan glioma modellerinde yapılmıştır. Tümörlerin davranışlarında tümörün in vivo mikro çevresel yapısı önemlidir. Dolayısıyla insan kaynaklı tümör rezeksiyon materyalleri kullanılarak yapılan çalışmaların tümör davranışı ile ilgili daha aydınlatıcı olacağını düşünmekteyiz. Yaptğımız çalışmada 29 hastadan elde edilen insan beyin tümör materyalleri ve perilezyoner normal beyin dokusu kullanıldı. PI3K/Akt yolağında rol oynadığı kabul edilen S1P1, S1PR3, SPHK1, CCN1, PLAU genlerinin ekspresyonları incelendi. Çalışmamıza dahil edilen genlerin hepsinde ekspresyon görüldü. Çalışma grubunda S1PR3’ün kontrol grubuna göre ekspresyonunun arttığı görüldü. Çalışma grubunda; S1PR1- S1PR3 ve CCN1- PLAU genleri arasında istatistiksel anlamlı yüksek oranda pozitif korelasyon görüldü. Kontrol grubunda; S1PR3- SPHK1, S1PR3- PLAU ve SPHK1- PLAU genleri arasında istatistiksel anlamlı yüksek oranda pozitif korelasyon görüldü. Ki67% değeri ile kontrol grubu CCN1 ekspresyonu arasında istatistiksel anlamlı yüksek oranda pozitif korelasyon görüldü. Kontrol grubunda, 9 ay ve daha kısa yaşayan hastalarda; S1PR1 ve CCN1 ekspresyonun azalmış olduğu görüldü. Kontrol grubundaki PLAU geninin nüks olan hastalarda daha az eksprese olduğu görüldü. Sonuç olarak, S1P1, S1PR3, SPHK1, CCN1, PLAU genlerinin ekspresyonunun insan gliomalarında nüks ve sağkalım süreleri ile ilişkili olabileceği düşünülmektedir.
Gliomas are histologically the most common type among primary brain tumors. The average patient survival time of these tumors are 1-2 years. These tumors have an invasive course, with recurrences in the early period. (2). Early relaps and short survival seen in HGGs, which contain genetic mutations and molecular abnormalities, are attributed to various mutations and expression changes in molecules that play a role in the invasion and neoangiogenesis pathways of the tumor (3). Although many studies have been conducted on different invasion and angiogenesis pathways of these tumors, which are a molecularly and genetically heterogeneous group, almost all of these studies have been conducted in cell cultures or on experimental animal glioma models. The in vivo microenvironmental structure of the tumor is important for the behavior of tumors. Therefore, we think that studies using humanderived tumor resection materials will be more enlightening about tumor behavior. In our study, human brain tumor materials and perilesional normal brain tissue obtained from 29 patients were used. We examined the expressions of S1P1, S1PR3, SPHK1, CCN1, PLAU genes, which are considered to play a role in the PI3K/Akt pathway. Expression of all of these genes were observed in our study. It was observed that the expression of S1PR3 has increased in the study group compared to the control group. There was a statistically significant high positive correlation between expression of S1PR1- S1PR3 and CCN1- PLAU genes in the study group. Also, there was a statistically significant high positive correlation between the expression of S1PR3- SPHK1, S1PR3- PLAU and SPHK1- PLAU genes. Furthermore, there was a statistically significant high positive correlation between CCN1 expression and Ki67% value in the control group. As for patients, the patients who lived less than 9 months; S1PR1 and CCN1 expression were decreased. In the control group it was observed that the PLAU gene expression in the control group was less in patients with relapse. These results suggest that S1P1, S1PR3, SPHK1, CCN1, PLAU genes may be associated with invasion, relapses, and survival.
Gliomas are histologically the most common type among primary brain tumors. The average patient survival time of these tumors are 1-2 years. These tumors have an invasive course, with recurrences in the early period. (2). Early relaps and short survival seen in HGGs, which contain genetic mutations and molecular abnormalities, are attributed to various mutations and expression changes in molecules that play a role in the invasion and neoangiogenesis pathways of the tumor (3). Although many studies have been conducted on different invasion and angiogenesis pathways of these tumors, which are a molecularly and genetically heterogeneous group, almost all of these studies have been conducted in cell cultures or on experimental animal glioma models. The in vivo microenvironmental structure of the tumor is important for the behavior of tumors. Therefore, we think that studies using humanderived tumor resection materials will be more enlightening about tumor behavior. In our study, human brain tumor materials and perilesional normal brain tissue obtained from 29 patients were used. We examined the expressions of S1P1, S1PR3, SPHK1, CCN1, PLAU genes, which are considered to play a role in the PI3K/Akt pathway. Expression of all of these genes were observed in our study. It was observed that the expression of S1PR3 has increased in the study group compared to the control group. There was a statistically significant high positive correlation between expression of S1PR1- S1PR3 and CCN1- PLAU genes in the study group. Also, there was a statistically significant high positive correlation between the expression of S1PR3- SPHK1, S1PR3- PLAU and SPHK1- PLAU genes. Furthermore, there was a statistically significant high positive correlation between CCN1 expression and Ki67% value in the control group. As for patients, the patients who lived less than 9 months; S1PR1 and CCN1 expression were decreased. In the control group it was observed that the PLAU gene expression in the control group was less in patients with relapse. These results suggest that S1P1, S1PR3, SPHK1, CCN1, PLAU genes may be associated with invasion, relapses, and survival.
Açıklama
Anahtar Kelimeler
Glioma, Sfingozin-1-fosfat, Neoplazm invazivitesi, Sfingozin kinaz, Ürokinaz plazminojen aktivatörü, Sphingosine-1-phosphate, Neoplasm invasiveness, Sphingosine kinase, Urokinase plasminogen activator
