Analiza ekspresije transkripcijskih čimbenika SOX2, OCT4 i NANOG i puta PI3K/AKT/BCL2 u malignom mezoteliomu pleure

doctoral thesis

• Title (english): Analysis of the transcription factors SOX2, OCT4 and NANOG expression and the PI3K/AKT/BCL2 pathway in malignant pleural mesothelioma
• Author: Fran Seiwerth
• Mentor: Marko Jakopović (mentor)
• Mentor: Filip Sedlić (komentor)
• Committee member: Miroslav Samaržija (predsjednik povjerenstva)
• Committee member: Božo Krušlin (član povjerenstva)
• Committee member: Tamara Nikuševa Martić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2023-12-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Cytology, Histology and Embryology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pathology
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Uvod: Maligni pleuralni mezoteliom je zloćudni tumor mezotelnog porijekla, čija dijagnostika i liječenje još uvijek predstavljaju izazov. OCT4, NANOG i SOX2 su čimbenici pluripotencije čija je aktivnost ključna za procese dijeljenja i sazrijevanja stanica tijekom embrionalnog razvoja, a koji se istražuju radi njihove uloge tokom onkogeneze. Signalni put PI3K/AKT/BCL2 jedna je od bolje proučenih kaskada prijenosa unutarstaničnih signala, čijom aktivnošću stanice raka izbjegavaju procese apoptoze i time si omogućavaju preživljenje.
Materijali i metode: U istraživanju su korišteni uzorci pacijenata s malignim pleuralnim mezoteliomom. Učinjene su imuohistokemijske i PCR analize radi detekcije proteina odnosno gena čimbenika pluripotencije OCT4, NANOG i SOX2 i puta PI3K/AKT/BCL2.
Rezultati: U ovom smo istraživanju dokazali aktivnost proteina i gena čimbenika pluripotencije u mezoteliomu pleure te u zdravom mezotelu. Aktivnost gena NANOG, SOX2 i OCT4 bila je viša u stanicama mezotela, dok je izraženost proteina bila viši u mezoteliomskim stanicama. Izraženost NANOG-a povezan je sa slabije diferenciranim podtipom mezotelioma. U istraživanju smo pokazali izraženost PI3K i AKT i BCL2 u mezoteliomu i u pleuri, pri čemu je aktivnost gena bila viša u stanicama pleure, a proteina AKT i BCL2 u stanicama mezotelioma.
Najlošije preživljenje imali su pacijenti sa sarkomatoidnim i pleomorfnim mezoteliomom, dok utjecaj izraženosti NANOG, OCT4 i SOX 2 te PI3K i AKT na preživljenje nije dokazan.
Zaključak: Zaključujemo kako su navedeni signalni mehanizmi aktivni u mezoteliomu pleure, a potrebna su dodatna istraživanja radi otkrivanja preciznih prediktivnih faktora u ovoj bolesti.

Abstract (english)

Introduction: Malignant pleural mesothelioma is a malignant tumor of mesothelial origin, the diagnosis and treatment of which still represent a challenge. OCT4, NANOG and SOX2 are pluripotency factors whose activity is crucial for the processes of cell division and maturation during embryonic development, and which are being investigated for their role during oncogenesis. The PI3K/AKT/BCL2 signaling pathway is one of the better-studied intracellular signal transmission cascades, with the activity of which cancer cells avoid the processes of apoptosis and thus enable their survival.
Materials and methods: The study used samples from patients with malignant pleural mesothelioma. Immunohistochemical and PCR analyzes were performed to detect proteins or genes of the pluripotency factors OCT4, NANOG and SOX2 and the PI3K/AKT/BCL2 pathway.
Results: In this study, we demonstrated the activity of pluripotency factor proteins and genes in pleural mesothelioma and in healthy mesothelium. NANOG, SOX2 and OCT4 gene activity was higher in mesothelial cells, while protein expression was higher in mesothelioma cells. NANOG expression is associated with a less differentiated subtype of mesothelioma. In the research, we showed the expression of PI3K and AKT and BCL2 in mesothelioma and in the pleura, whereby gene activity was higher in pleural cells, and AKT and BCL2 proteins in mesothelioma cells.
Patients with sarcomatoid and pleomorphic mesothelioma had the worst survival, while the influence of the expression of NANOG, OCT4 and SOX 2 and PI3K and AKT on survival was not proven.
Conclusion: We conclude that the above signaling mechanisms are active in pleural mesothelioma, and additional research is needed to reveal precise predictive factors in this disease.

• Keywords: Ljudi; Trudnoća; Žena; Mezoteliom; maligni; AKT geni; PI3K protein; Pleura; BCL2 proteini; Mezoteliom; Transformacija stanica; neoplastična; Prijenos signala; Lančana reakcija polimerazom; Apoptoza; Dijeljenje stanica; Epitel; Embrionalni razvoj
• Keywords (english): Humans; Pregnancy; Female; Mesothelioma; Malignant; AKT genes; PI3K protein; Pleura; BCL2 proteins; Mesothelioma; Cell Transformation; Neoplastic; Signal Transduction; Polymerase Chain Reaction; Apoptosis; Cell Division; Epithelium; Embryonic Development
• Language: croatian
• URN:NBN: urn:nbn:hr:105:460983
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 86 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-12-14 08:35:44