| Abstract | Uvod: Stanična senescencija je proces u kojem se stanice trajno prestaju dijeliti, a koji ima ključnu ulogu u kontroli tumorskog rasta i odgovoru na terapiju. Gliomi su najčešći primarni tumori središnjeg živčanog sustava, a prognoza im je često nepovoljna zbog agresivnog kliničkog tijeka i česte rekurencije nakon terapije. Sve više istraživanja upućuje na značaj senescentnih stanica glioma na takav klinički tijek ovih tumora. Cilj ove studije je analizirati učestalost i tip promjena gena uključenih u staničnu senescenciju u različitim tipovima glioma.
Materijali i metode: Analizirali smo 3425 uzoraka glioma koristeći podatke s cBioPortala za genomiku tumora. Odabrali smo 10 najčešće promijenjenih gena povezanih sa senescencijom: TP53, CDKN2A, EGFR, ATM, TNFRSF1A, IGFBP7, TNFRSF11B, TP53BP1, HGF i SERPINE1. In silico analiza podataka uključivala je određivanje učestalosti mutacija, amplifikacija, delecija i višestrukih promjena u svakom tipu glioma.
Rezultati: Rezultati su pokazali da su u ukupnom uzorku TP53, CDKN2A i EGFR najčešće promijenjeni geni. CDKN2A, EGFR, ATM, IGFBP7, TP53BP1 i HGF su imali veći postotak promjena u gliomima visokog stupnja (HGG), dok su TP53, TNFRSF1A, TNFRSF11B i SERPINE1 bili češće promijenjeni u gliomima nižeg stupnja (LGG). Statistički značajna razlika u promjenama između HGG i LGG skupina je utvrđena za TP53, CDKN2A, EGFR, IGFBP7 te TNFRSF11B.
Zaključak: Pokazali smo kako su proučavani geni češće promijenjeni u gliomima viših gradusa. Obrasci promjena odgovaraju dosadašnjim spoznajama iz literature. Ovi nalazi naglašavaju važnost specifičnih genetskih promjena u regulaciji stanične senescencije i njihov utjecaj na malignost glioma. Daljnja istraživanja su potrebna kako bi se bolje razumjeli mehanizmi kojima ovi geni utječu na senescenciju i klinički tijek glioma. |
| Abstract (english) | Introduction: Cellular senescence is a process in which cells permanently cease to divide, playing a key role in controlling tumor growth and response to therapy. Gliomas are the most common primary tumors of the central nervous system, often with a poor prognosis due to aggressive clinical behavior and frequent recurrence after therapy. Increasing research indicates the significance of senescent glioma cells in shaping the clinical profile of these tumors. The aim of this study was to analyze the frequency and type of alterations in genes involved in cellular senescence in different types of gliomas.
Materials and Methods: We analyzed 3425 glioma samples using data from the cBioPortal for Cancer Genomics. We selected and studied the 10 most frequently altered genes related to senescence: TP53, CDKN2A, EGFR, ATM, TNFRSF1A, IGFBP7, TNFRSF11B, TP53BP1, HGF and SERPINE1. Data analysis included determining the frequency of mutations, amplifications, deletions, and multiple alterations in each type of glioma.
Results: The results showed that TP53, CDKN2A, and EGFR were the most frequently altered genes. CDKN2A, EGFR, ATM, IGFBP7, TP53BP1, and HGF had a higher percentage of alterations in high-grade gliomas (HGG), while TP53, TNFRSF1A, TNFRSF11B and SERPINE1 were more frequently altered in low-grade gliomas (LGG). A statistically significant difference in alterations between the HGG and LGG groups was found for TP53, CDKN2A, EGFR, IGFBP7 and TNFRSF11B.
Conclusion: We have shown that the studied genes are more frequently altered in high-grade gliomas. The patterns of alterations correspond to the existing knowledge in the literature. The results highlight the importance of specific gene changes in cellular senescence and their association to glioma grade. Further research is needed to better understand the mechanisms by which these genes influence senescence and the clinical course of gliomas. |
