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Title:Validacija klinično pomembnih transkripcijskih biooznačevalcev v krvnih vzorcih pred in po zdravljenju trojno negativnega raka dojke : magistrsko delo
Authors:ID Konajzler, Anja (Author)
ID Potočnik, Uroš (Mentor) More about this mentor... New window
ID Čelešnik, Helena Sabina (Comentor)
ID Arko, Darja (Comentor)
Files:.pdf MAG_Konajzler_Anja_2022.pdf (3,60 MB)
MD5: 9665ADC1C0C544C296D159C0DE66D255
 
Language:Slovenian
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:FKKT - Faculty of Chemistry and Chemical Engineering
Abstract:Rak dojke (RD) je najpogostejši rak pri ženskah in drugi najpogostejši vzrok smrti zaradi raka pri ženskah. Gre za maligno obolenje, ki izvira iz tkiva dojke, najpogosteje iz notranje obloge mlečnih vodov ali režnjev, ki vode oskrbujejo z mlekom. Eden izmed podtipov raka dojke je trojno negativni rak dojke (TNRD), za katerega je značilno, da nima ekspresije ER in PR in nima amplifikacije HER2, ter da je zelo invaziven in povezan s slabo prognozo in visoko umrljivostjo. Spremenjeno izražanje genov CXCR4, THBS1 in miR-137 so predhodno povezali s TNRD. Namen naše študije je bil testirati in validirati njihovo uporabnost kot potencialni krvni biomarkerji za trojno negativni rak dojke. V primerjavi s tkivnimi označevalci imajo krvni biološki označevalci pomembno prednost, da so manj invazivni. Iz 210 vzorcev mononuklearnih celic periferne krvi (PBMC) odvzetih bolnicam z rakom dojke pred zdravljenjem, 28 vzorcev plazme (13 pred zdravljenjem, 15 po zdravljenju) ter 25 vzorcev krvnih PBMC zdravih kontrol smo izolirali RNA za analizo izražanja genov z metodo RT-qPCR. Plazemski vzorci pred in po zdravljenju TNRD so bili zanimivi s stališča spremljanja terapije. Analiza izražanja CXCR4 v imunskih celicah PBMC je pri pacientkah z rakom dojke pred terapijo odkrila zanimive rezultate. Izražanje CXCR4 je bilo značilno povišano pri tistih bolnicah, ki so imele invazivni duktalni karcinom (IDC), v primerjavi s tistimi, ki so imele invazivni lobularni karcinom (ILC). To nakazuje na potencialno uporabnost merjenja izražanja CXCR4 v krvi kot označevalca za IDC. Ugotovili smo tudi, da imajo pacientke, pri katerih rakave celice izražajo PR, značilno povečano izražanje CXCR4 v krvnih imunskih celicah. Teh izsledkov nismo zasledili v objavljeni literaturi in predstavljajo nove ugotovitve pri raku dojke. Analiza THBS1 v frakciji PBMC pacientk z rakom dojke pred terapijo je pokazala povišano izražanje tega gena v skupini TNRD v primerjavi z ostalimi podtipi raka dojke in zdravimi kontrolami, vendar v naši kohorti razlika v izražanju ni dosegla statistične signifikance. Pri analizi prekurzorske oblike miR-137 v plazmi pred in po terapiji smo naleteli na tehnične težave, zato bo za to analizo potrebna dodatna optimizacija postopka.
Keywords:rak dojk, TNRD, PBMC, CXCR4, THBS1, miR-137, genska ekspresija
Place of publishing:Maribor
Place of performance:Maribor
Publisher:[A. Konajzler]
Year of publishing:2022
Number of pages:1 spletni vir (1 datoteka PDF (XII, 55 f.))
PID:20.500.12556/DKUM-82961 New window
UDC:575.117:618.19-006(043.2)
COBISS.SI-ID:132426243 New window
Publication date in DKUM:26.09.2022
Views:641
Downloads:60
Metadata:XML DC-XML DC-RDF
Categories:KTFMB - FKKT
:
KONAJZLER, Anja, 2022, Validacija klinično pomembnih transkripcijskih biooznačevalcev v krvnih vzorcih pred in po zdravljenju trojno negativnega raka dojke : magistrsko delo [online]. Master’s thesis. Maribor : A. Konajzler. [Accessed 27 March 2025]. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=82961
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Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:12.09.2022

Secondary language

Language:English
Title:Validation of clinically relevant transcriptional biomarkers in pre- and post-treatment blood samples from triple negative breast cancer patients
Abstract:Breast cancer (BC) is the most common cancer and the second most common cause of death from cancer in women. BC is a malignant disease that originates from the breast tissue, most often from the inner lining of the milk ducts or lobes that supply the ducts with milk. One of the subtypes of breast cancer is the triple negative breast cancer (TNBC), which does not express ER and PR and does not have HER2 amplification. This subtype is highly invasive and associated with poor prognosis and high mortality. Altered expression of CXCR4, THBS1 and miR-137 has previously been associated with TNBC. The aim of our study was to analyze and validate the potential utility of expression of these genes as blood biomarkers for TNBC. Compared to tissue markers, blood biomarkers have the important advantage of being less invasive. RNA was isolated for RT-qPCR gene expression analysis from 210 samples of peripheral blood mononuclear cells (PBMCs) taken from treatment-naive breast cancer patients, 28 plasma samples (13 before treatment, 15 after treatment) and 25 PBMC samples taken from healty controls. Plasma samples before and after TNBC treatment were of interest from the standpoint of therapy monitoring. Analysis of CXCR4 expression in imune PBMC cells from treatment-naive BC patients revealed interesting findings. CXCR4 expression was significantly elevated in patients with invasive ductal carcinoma (IDC) compared to those with invasive lobular carcinoma (ILC), suggesting that CXCR4 expression in blood cells may be useful as a marker for IDC. We also observed that patients whose cancer cells express PR had a characteristically increased expression of CXCR4 in blood immune cells. To our knowledge, these observations have not been published elsewhere and represent new findings in breast cancer. Analysis of THBS1 in the PBMC fraction of treatment-naive BC patients showed elevated expression of this gene in the TNBC group compared to other breast cancer subtypes and healthy controls, but in our cohort the expression difference did not reach statistical significance. When analyzing expression of the precursor form of miR-137 in plasma samples taken before and after therapy, we encountered technical difficulties, therefore this analysis will require further process optimization
Keywords:breast cancer, TNBC, PBMC, CXCR4, THBS1, miR-137, gene expression


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