diplomsko delo univerzitetnega študijskega programa I. stopnje
Anja Vrbek (Author), Uroš Potočnik (Mentor), Bogdan Čizmarevič (Co-mentor), Tomaž Büdefeld (Co-mentor)

Abstract

Receptor ERBB3 (angl. erb-b2 receptor tyrosine kinase 3) uravnava rast, proliferacijo, preživetje celic in angiogenezo. Njegovo spremenjeno aktivnost povezujejo z nastankom in razvojem raka glave in vratu (angl. head and neck cancer - HNC). Gen ERBB3 zraven receptorja ERBB3 kodira še manjše topne, sekretorne beljakovine (sERBB3), katerih vloga v patogenezi HNC ni povsem pojasnjena. Za boljšo pojasnitev vloge ERBB3 in sERBB3 pri HNC, smo v diplomski nalogi na vzorcu 34 bolnikov z RT-qPCR proučili izražanje mRNA za receptor ERBB3 in sekretorno beljakovino velikosti 22 kDa p22-sERBB3 ter njuno izražanje opisali iz stališča klinično-patoloških značilnosti HNC. Tako ERBB3 kot p22-sERBB3 sta bila izražena v tumorskem in zdravem tkivu, pri čemer je bilo za tumorsko tkivo značilno nižje izražanje ERBB3 (p < 0,001) in p22-sERBB3 (p < 0,05) v primerjavi z zdravim tkivom. Prav tako je bilo izražanje ERBB3 višje (p < 0,001) od izražanja p22-sERBB3. Ugotovili smo tudi pozitivno korelacijo med izražanjem ERBB3 in p22-sERBB3 tako v tumorskem (p = 0,001) kot zdravem (p = 0,001) tkivu. Izražanje p22-sERBB3 je bilo višje (p < 0,05) pri rakih ustne votline z ustnicami v primerjavi z raki grla in žrela. Za razliko od p22-ERBB3 pa vpliva mesta nastanka tumorja na izražanje ERBB3 nismo ugotovili. Parcialna analiza izražanja ERBB3 je pokazala na višje izražanje ERBB3 v zdravem kot tumorskem tkivu pri rakih grla (p < 0,05) in žrela (p < 0,001), ne pa pri rakih ustne votline z ustnicami. Tumorji z limfovaskularno invazijo so imeli statistično značilno nižje izražanje ERBB3 (p < 0,05) in p22-sERBB3 (p < 0,05) v tumorskem kot zdravem tkivu, medtem ko pri tumorjih brez limfovakularne invazije omenjenih razlik nismo ugotovili zaradi povišanega izražanja ERBB3 oziroma p22-sERBB3 v tumorskem tkivu. Pri tumorjih brez HPV-16 je bilo izražanje ERBB3 nižje (p < 0,05) v primerjavi z zdravim tkivom, ta razlika pa pri tumorjih, okuženih s HPV-16, ni bila prisotna zaradi povišanega izražanja ERBB3 v tumorskem tkivu. Analiza izražanja ERBB3 in p22-sERBB3 po stadijih tumorjev je pokazala, da so bolj razviti raki imeli višje izražanje ERBB3 (cT3: p < 0,01; cT4: p < 0,05; pT2: p < 0,05; pT3: p < 0,01; pT4: p < 0,05) in p22-sERBB3 (cT4 in pT4, oba p < 0,05) v zdravem kot tumorskem tkivu. Vpliva kajenja in uživanja alkohola na izražanje ERBB3 in p22-sERBB3 v zdravem in tumorskem tkivu nismo ugotovili. Naši rezultati kažejo na vlogo mRNA za topno, sekretorno beljakovino p22-sERBB3 pri patogenezi raka glave in vratu. Izražanje ERBB3 je bilo pri tumorjih raka glave in vratu znižano v primerjavi z zdravim tkivom, na njegovo izražanje pa so vplivali prisotnost limfovaskularne invazije, gradus tumorja in okužba s HPV-16.

Keywords

receptor ERBB3;beljakovina p22-sERBB3;rak glave in vratu;podtip HPV-16;invazija;reakcija RT-qPCR;diplomske naloge;

Data

Language: Slovenian
Year of publishing:
Typology: 2.11 - Undergraduate Thesis
Organization: UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher: [A. Vrbek]
UDC: 616.006.04(043.2)
COBISS: 103837955 Link will open in a new window
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Downloads: 42
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Other data

Secondary language: English
Secondary title: Expression of mRNA isoforms encoding ERBB3 receptor and secretory protein p22-sERBB3 in head and neck cancer patients
Secondary abstract: ERBB3 (erb-b2 receptor tyrosine kinase 3) receptor regulates cell growth, proliferation, survival and angiogenesis. Its altered activity has been associated with the occurrence and development of head and neck cancer (HNC). In addition to the ERBB3 receptor, the ERBB3 gene encodes small soluble, secretory proteins (sERBB3) whose role in the pathogenesis of HNC is not fully understood. To better elucidate the role of ERBB3 and sERBB3 in HNC, we examined the mRNA expression of the ERBB3 receptor and the 22 kDa secretory protein p22 sERBB3 in a cohort of 34 patients by RT-qPCR and characterized their expression in terms of clinicopathological features of HNC. Both ERBB3 and p22-sERBB3 were expressed in tumor and normal tissue, with tumor tissue having a significantly lower expression of ERBB3 (p < 0,001) and p22-sERBB3 (p < 0,05) than normal tissue. ERBB3 expression was also significantly higher (p < 0,001) than p22-sERBB3 expression. There was also a positive correlation between ERBB3 and p22-sERBB3 expression in tumor (p = 0,001) and normal (p = 0,001) tissue. The expression of p22-sERBB3 was significantly higher (p < 0,05) in cancers of the lips and oral cavity compared to laryngeal and pharyngeal cancers. In contrast to p22-ERBB3, ERBB3 expression did not differ between the tumor sites. Analysis of ERBB3 expression by tumor site showed significantly higher ERBB3 expression in normal than in tumor tissue in laryngeal (p < 0,05) and pharyngeal (p < 0,001) cancers, but not in oral cavity and lip cancers. Tumours with lymphovascular invasion had significantly lower expression of ERBB3 (p < 0,05) and p22-sERBB3 (p < 0,05) in tumor than normal tissue, whereas these differences were not observed in tumours without lymphovascular invasion due to increased expression of ERBB3 and p22-sERBB3 in tumor tissue, respectively. In HPV-16 negative tumours, ERBB3 expression was significantly lower (p < 0,05) in tumour than normal tissue, whereas this difference was not observed in HPV-16 positive tumours due to increased ERBB3 expression in tumour tissue. Analysis of ERBB3 and p22-sERBB3 expression by tumour stage showed significantly higher ERBB3 (cT3: p < 0,01; cT4: p < 0,05; pT2: p < 0,05; pT3: p < 0,01; pT4: p < 0,05) and p22-sERBB3 (cT4 and pT4, both p < 0,05) expression in normal than tumour tissue in higher-grade cancers. We found no effect of smoking and alcohol consumption on ERBB3 and p22-sERBB3 expression in HNC. Our results suggest a role for the p22-sERBB3 in the pathogenesis of head and neck cancer. ERBB3 expression was downregulated in head and neck cancer compared to normal tissue, and its expression was influenced by the presence of lymphovascular invasion, tumour grade and HPV-16 infection.
Secondary keywords: ERBB3;p22-sERBB3;head and neck cancer;HPV-16;invasion;RT-qPCR;
Type (COBISS): Bachelor thesis/paper
Thesis comment: Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages: 1 spletni vir (1 datoteka PDF (IX, 35 f.))
ID: 14796526