Izražanje genov za DNA in RNA metilaze in demetilaze pri bolnikih z rakom glave in vratu

diplomsko delo visokošolskega strokovnega študijskega programa I. stopnje

Karmen Zorič (Avtor), Uroš Potočnik (Mentor), Boštjan Lanišnik (Komentor), Larisa Goričan (Komentor)

Povzetek

Letna incidenca raka glave in vratu (RGV, angl. Head and Neck cancer, HNC) znaša okoli 700 000 novo odkritih primerov po celotnem svetu, kar ga izmed vseh bolezni uvršča na šesto mesto. Najpogostejša oblika RGV je ploščatocelični karcinom, ki predstavlja 85 % vseh primerov RGV. Za RGV so značilni različni simptomi, ki tudi pomagajo pri odkrivanju bolezni. Zdravljenje temelji na določitvi stopnje napredovanja bolezni. Epigenetske spremembe, kot sta DNA in RNA metilacija, spadajo med značilne spremembe karcinoma. Ker je ekspresija genov metilaz in demetilaz v tkivih RGV še vedno slabo raziskana, smo v sklopu diplomskega dela v tkivih bolnikov RGV dodatno proučili gensko ekspresijo nabora DNA in RNA metilaz in demetilaz ter njihovo ekspresijo povezali s klinično patološkimi značilnostmi tumorjev glave in vratu ter jih izkoristili za napoved razvoja, zdravljenja in ponovitve bolezni. Tako smo v zdravem in tumorskem tkivu 34 bolnikov z rakom glave in vratu, s pomočjo metode RT-qPCR, proučili izražanje genov DNMT1, DNMT3A, DNMT3B, TET1, TET2, TET3 in TRDMT1. Ugotovili smo povezavo med izražanjem TRDMT1, kliničnimi parametri in dejavniki tveganja, vključno z mestom nastanka tumorja, kadilskim statusom, uživanjem alkohola ter HPV okužbo. Stopnja izražanja TRDMT1 je bila povezana z napredovanjem/agresivnostjo bolezni, in sicer se z znižanjem TRDMT1 stopnja napredovanja agresivnosti viša. Pri analizi izražanja DNA metilaz in demetilaz v odvisnosti od prisotnosti ali odsotnosti zasevkov v področnih bezgavkah v tumorskem tkivu smo ugotovili trend povišanega izražanja DNA metilaz in demetilaz v zgodnjih stadijih ter trend znižanega izražanja DNA metilaz in demetilaz v poznih stadijih. V ta namen bi bilo smiselno raziskavo razširiti na večje število vzorcev, s čimer bi se posledično povečala statistična moč analize, ki bi lahko prispevala k razjasnitvi vloge izražanja DNA in RNA metilaz ter demetilaz kot potencialnih kazalcev za klasifikacijo bolnikov in določitev ocene napredovanja bolezni.

Ključne besede

rak glave in vratu;metilaze;demetilaze;relativna genska ekspresija;tumorsko tkivo;diplomske naloge;

Podatki

Jezik:	Slovenski jezik
Leto izida:	2022
Tipologija:	2.11 - Diplomsko delo
Organizacija:	UM FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Založnik:	[K. Zorič]
UDK:	575.117:616.91/.93-006.6(043.2)
COBISS:	130424067
Št. ogledov:	130
Št. prenosov:	36
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Angleški jezik
Sekundarni naslov:	Gene expression of DNA and RNA methylases and demethylases in head and neck cancer patients
Sekundarni povzetek:	The annual incidence of head and neck cancer (HNC) is around 700 000 newly diagnosed cases worldwide, ranking it sixth among all diseases. The most common form of HNC is squamous cell carcinoma, which accounts for 85% of all HNC cases. HNC is characterised by a variety of symptoms, which also help in the detection of the disease. Treatment is based on the stage of disease progression. Epigenetic changes such as DNA and RNA methylation are among the characteristic changes of carcinoma. As the gene expression of methylases and demethylases in HNC tissues is still poorly understood, as part of our thesis, we further investigated the gene expression of a set of DNA and RNA methylases and demethylases in HNC tissues and correlated their expression with clinicopathological features of head and neck tumors, and exploited them to predict the development, treatment and recurrence of the disease. Thus, the expression of DNMT1, DNMT3A, DNMT3B, TET1, TET2, TET3 and TRDMT1 genes was investigated in healthy and tumor tissue from 34 HNC patients by RT-qPCR. We found an association between TRDMT1 expression, clinical parameters and risk factors including tumor site, smoking status, alcohol consumption and HPV infection. TRDMT1 expression level was associated with disease progression/aggressiveness, with an increase in aggressiveness progression with TRDMT1 downregulation. When analysing the expression of DNA methylases and demethylases in relation to the presence or absence of lymph node involvement in tumor tissue, we found a trend towards increased expression of DNA methylases and demethylases in early stages, and a trend towards decreased expression of DNA methylases and demethylases in late stages. To this end, it would be worthwhile to extend the study to a larger number of samples, which would consequently increase the statistical power of the analysis, which could contribute to clarifying the role of the expression of DNA and RNA methylases and demethylases as potential indicators for classifying patients and assessing disease progression.
Sekundarne ključne besede:	head and neck cancer;methylases;demethylases;relative gene expression;tumor tissue;
Vrsta dela (COBISS):	Diplomsko delo/naloga
Komentar na gradivo:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Strani:	1 spletni vir (1 datoteka PDF (X, 55 f.))
ID:	16260490