20.500.12556/DKUM-99623 Izražanje genov imunskih kontrolnih točk pri raku dojke Immune checkpoint gene expression in breast cancer Imunski sistem ima pomembno vlogo pri razvoju in napredovanju raka dojke, pri čemer imajo ključno vlogo imunske kontrolne točke. Rak dojke je heterogena bolezen, pri kateri se posamezni podtipi razlikujejo tudi v značilnostih imunskega odziva. Namen diplomskega dela je bil določiti relativno izražanje genov imunskih kontrolnih točk PDCD1, CD274, CTLA4 in LAG3 v perifernih krvnih mononuklearnih celicah (PBMC) bolnic z rakom dojke in zdravih kontrol ter proučiti razlike v njihovem izražanju med podtipi raka dojke. Izražanje genov smo določili z metodo kvantitativne verižne reakcije s polimerazo v realnem času (qPCR). Analizirali smo vzorce bolnic s trojno negativnim rakom dojke (TNRD), luminalnim A, luminalnim B in HER2-pozitivnim podtipom raka dojke ter zdrave kontrole, pri čemer je bila razvrstitev podtipov izvedena na podlagi imunohistokemične klasifikacije. Eksperimentalne rezultate smo dopolnili z analizo javno dostopnih podatkov sekvenciranja RNK iz podatkovne baze bc-GenExMiner, kjer smo proučili izražanje istih genov v tumorskem tkivu glede na molekularne podtipe raka dojke. Pri bolnicah z rakom dojke je bilo izražanje genov PDCD1, CD274 in LAG3 statistično značilno višje kot pri zdravih kontrolah, medtem ko pri CTLA4 značilne razlike ni bilo. Med podtipi raka dojke je bilo izražanje PDCD1, CD274 in LAG3 statistično značilno nižje pri TNRD v primerjavi z Ne-TNRD, medtem ko pri CTLA4 razlika ni bila značilna. Primerjava rezultatov PBMC z izražanjem v tumorskem tkivu na podlagi podatkov iz spletne podatkovne baze bc-GenExMiner je pokazala, da so bili trendi izražanja različni in v nasprotni smeri kot v PBMC. Rezultati tako kažejo, da je izražanje genov imunskih kontrolnih točk v PBMC različno med kontrolami in rakom dojke. Opažene razlike med podtipi raka dojke pa poudarjajo heterogenost bolezni in kompleksnost imunskega odziva. The immune system plays an important role in the development and progression of breast cancer, with immune checkpoint molecules having a key role. Breast cancer is a heterogeneous disease in which individual subtypes also differ in the characteristics of the immune response. The aim of this thesis was to determine the relative expression of the immune checkpoint genes PDCD1, CD274, CTLA4, and LAG3 in peripheral blood mononuclear cells (PBMCs) of breast cancer patients and healthy controls, and to investigate differences in their expression among breast cancer subtypes. Gene expression was determined using quantitative PCR (qPCR). Samples from patients with triple-negative breast cancer (TNBC), luminal A, luminal B, and HER2-positive breast cancer subtypes, as well as healthy controls, were analysed. The classification of breast cancer subtypes was based on immunohistochemical classification. The experimental results were complemented by an analysis of publicly available RNA sequencing data from the bc-GenExMiner database, in which the expression of the same genes in tumour tissue was investigated according to the molecular subtypes of breast cancer. In breast cancer patients, the expression of PDCD1, CD274, and LAG3 was significantly higher than in healthy controls, whereas no significant difference was observed for CTLA4. Among breast cancer subtypes, the expression of PDCD1, CD274, and LAG3 was significantly lower in TNBC compared with non-TNBC, whereas no significant difference was observed for CTLA4. Comparison of the PBMC results with gene expression in tumour tissue based on data from the bc-GenExMiner database showed that the expression trends differed and were in the opposite direction to those observed in PBMCs. These results indicate that the expression of immune checkpoint genes in PBMCs differs between healthy controls and breast cancer patients. The observed differences among breast cancer subtypes further highlight the heterogeneity of the disease and the complexity of the immune response. rak dojke imunske kontrolne točke PBMC qPCR PDCD1 CD274 LAG3 CTLA4 breast cancer immune checkpoints PBMCs qPCR PDCD1 CD274 LAG3 CTLA4 true true false Slovenski jezik Angleški jezik Diplomsko delo/naloga 2026-08-21 10:48:22 2026-09-23 11:44:42 2026-09-24 03:07:30 0000-00-00 00:00:00 2026 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 UN_Mlakar_Sergeja_2026.pdf UN_Mlakar_Sergeja_2026.pdf 1 6FD0CD7841DA1B1C81CFB9DF14A42A3D 88dc9fa73e0feaa61c524badacb542e66384287cefc1c56273bcf5534143a2a4 a286a817-b70e-11f1-a2e0-00155d0001be https://dk.um.si/Dokument.php?lang=slv&id=213228 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0