Ekspresija gena HNF1A u hepatocelularnom karcinomu

master's thesis

• Title (english): EHNF1A gene expression in hepatocellular carcinom
• Author: Petra Leko
• Mentor: Petra Korać (mentor)
• Committee member: Gordana Lacković-Venturin (predsjednik povjerenstva)
• Committee member: Petra Korać (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Antun Alegro (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2015-02-26, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Hepatocelularni karcinom (HCC) je primarni maligni tumor jetre. Unatoč dostupnosti različitih terapija, bolest se ponovno vraća u približno 80% slučajeva, a u uznapredovanom stadiju bolesti izbor terapije je limitiran. Poboljšanje razumijevanja molekularne osnove karcinogeneze HCC-a osnova je za poboljšanje razvoja efikasnijih terapija. HCC-u u velikom broju slučajeva prethodi ciroza. Oba ova stanja nastaju kao posljedica promjene ekspresije brojnih gena od kojih je barem dio reguliran transkripcijskim aktivatorom hepatocita HNF1. Gen HNF1A ključan je za održavanje funkcije jetre budući da regulira ekspresiju mnogih gena uključenih u procese proliferacije, angiogeneze, epitelno-mezenhimske tranzicije, fukozilacije te glikolize, lipogeneze i glukoneogeneze. Utišana ekspresija gena HNF1A povezana je s deregulacijom tih signalnih putova što je dovelo do pretpostavke da bi mogla biti povezana i s nastankom i progresijom HCC-a. Kako bi se utvrdila potencijalna razlika u razini ekspresije gena HNF1A iz uzoraka tumorskog tkiva HCC-a i okolnog tkiva jetre koje u najvećem broju slučajeva predstavlja cirozu, izolirana je RNA te reverznom transkripcijom prevedena u cDNA. Razina ekspresije gena određena je lančanom reakcijom polimerazom u stvarnom vremenu, a dobiveni podaci analizirani su u odnosu na podatke o razvoju i progresiji bolesti dostupne za navedenu skupinu ispitanika. Dobiveni rezultati pokazuju da ne postoji značajna razlika u razini ekspresije gena HNF1A u tumorskom tkivu i u okolnom tkivu jetre, sugerirajući da promjena ekspresije gena nije uključena u razvoj HCC-a iz predkarcinomskog stadija.

Abstract (english)

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Despite the multiple treatment options the recurrence of the disease is about 80 % and in advanced stages treatment options are limited. Understanding the underlying molecular mechanisms of carcinogenesis of HCC is the basis for improving the development of more effective therapies. In many cases HCC is preceded by cirrhosis. Both of these conditions result from changes in the expression levels of many genes, part of which are regulated by the hepatocyte transcriptional activator HNF1. The gen HNF1A is essential for maintaining liver function, since it regulates the expression of many genes involved in the processes of cell proliferation, angiogenesis, epithelial to mesenchymal transition, fucosylation, glycolysis, lipogenesis and gluconeogenesis. Decreased expression of HNF1A is associated with deregulation of these signaling pathways which leads to the hypothesis that it could be associated with the development and progression of HCC. In order to evaluate potential differences of HNF1A expression levels in tumor tissue and surrounding liver tissue which, in most cases represent cirrhosis, RNA was isolated from tissue samples of patients diagnosed with HCC and converted to cDNA by reverse transcription. The level of gene expression was determined by quantitative real time polymerase chain reaction. The obtained data were analyzed in relation to information about the development and progression of the disease, available for patients included in this study. The results showed that there is no significant difference in the level of HNF1A expression in tumor tissue and surrounding tissue of the liver, suggesting that the change in HNF1A expression is not one of the key steps involved in development of HCC from precancerous tissue.

• Keywords: hepatocelulatni karcinom; HNF1A; ciroza; -fetoprotein
• Keywords (english): hepatocellular carcinoma; HNF1A; cirrhosis; -fetoprotein
• Language: croatian
• URN:NBN: urn:nbn:hr:217:184346
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2017-04-21 11:28:08