Title Prognostička vrijednost proteomskoga profila dobro diferenciranih papilarnih karcinoma štitnjače Title (english) Prognostic significance of the proteome profile of well differentiated papillary thyroid carcinoma Author Filip Matovinović Mentor Vladimir Bedeković (mentor)Mentor Lovorka Grgurević (komentor)Committee member Hrvoje Čupić (predsjednik povjerenstva)Committee member Ruđer Novak (član povjerenstva)Committee member Andro Košec (član povjerenstva)Granter University of Zagreb Defense date and country 2023-01-18, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 616 - Pathology. Clinical medicine Abstract Povećana incidencija papilarnog karcinoma štitnjače, a prije svega papilarnog mikrokarcinoma velik je dijagnostičko-terapijski problem te opterećenje za pacijente i zdravstveni sustav. Iako se papilarni karcinomi smatraju karcinomima niske smrtnosti, oni nose značajan rizik od regionalnog širenja bolesti, što dovodi do povećanog morbiditeta, s obzirom na to da je primarni način liječenja ove bolesti kirurški. Trenutačno ne postoje biljezi bolesti koji bi preoperativno mogli, s visokom specifičnošću i osjetljivošću, diferencirati indolentnu bolest od one agresivnije. Takva preoperativna diferencijacija omogućila bi optimalno planiranje liječenja uz značajno smanjenje opterećenja i morbiditeta samog liječenja.
Prema svim trenutačno prihvaćenima stratifikacijama papilarni mikrokarcinomi pripadaju skupini niskorizičnih papilarnih karcinoma, no ipak su u znatnoj mjeri skloni regionalnom širenju bolesti. U ovom radu analiziran je proteomski profil 30 papilarnih mikrokarcinoma – 15 koji u trenutku operativnog liječenja nisu dali metastaze i 15 koji su dali metastaze u lateralne regije vrata. Proteomski profil papilarnih mikrokarcinoma pokazao je značajnu razliku u izraţaju proteina i gena ovisno o promatranoj skupini.
U skupini s metastazama, utvrĎeno je više proteina koji bi mogli biti povezani s metastaziranjem i agresivnijim biološkim ponašanjem. To su ubikvitin konjugirajući enzim E2 varijanta 1, natrij- i klor-ovisan taurinski transporter, sindekani -2 i -4, alfa-1-antiripsin, histon-lizin N-metiltransferaza 2C i citrat sintaza. TakoĎer je u skupini s metastazama identificirana pojačana ekspresija triju gena: PLAU, ATF1 i CREB1, koji potencijalno imaju ulogu u agresivnijem ponašanju odreĎenih papilarnih mikrokarcinoma.
Budući da je ovo prvi proteomski rad, prema našim spoznajama, koji je usporeĎivao papilarne mikrokarcinome koji su dali regionalne metastaze i one koji nisu, rezultati ovog rada pridonijeli su produbljivanju znanja o proteinskom izraţaju i potencijalnoj patofiziološkoj ulozi izraţenih proteina u metastaziranju papilarnog mikrokarcinoma štitnjače. TakoĎer, ovim radom postavljeni su i temelji za buduća istraţivanja.
Abstract (english) The increasing incidence of papillary thyroid cancer, primarily papillary microcarcinoma, represents a significant diagnostic and therapeutic problem and a burden for patients and the health care system. Although papillary carcinomas are considered to be cancers of low mortality, they carry a significant risk of regional spread of disease, which consequently leads to increased morbidity, given that the primary method of treatment is surgery. Currently, there are no biomarkers that could, preoperatively, with high specificity and sensitivity, differentiate an indolent disease from a more aggressive one. Such preoperative differentiation would enable optimal treatment planning with a significant reduction in burden and morbidity of the treatment itself. According to all currently accepted classifications, papillary microcarcinomas belong to the group of low-risk papillary carcinomas, but they are still significantly prone to regional spread of disease. In this thesis, the proteomic profile of 30 papillary microcarcinomas was analyzed – 15 that did not metastasize at the time of surgical treatment and 15 that metastasized to the lateral regions of the neck. The proteomic profile of papillary microcarcinomas showed a significant difference in protein and gene expression, depending on the observed group.
In the group with metastases, certain proteins were identified that could lead to metastatic disease and more aggressive biological behavior. These are ubiquitin conjugating enzyme E2 variant 1, sodium- and chlorine-dependent taurine transporter, syndecans -2 and -4, alpha-1-antirypsin, histone-lysine N-methyltransferase 2C and citrate synthase. Increased expression of three genes, PLAU, ATF1 and CREB1, was also identified in the group with metastases, which could also potentially play a role in the more aggressive behavior of certain papillary microcarcinomas.
Considering the results and the fact that, to our knowledge, this is the first proteomic thesis that compared papillary microcarcinomas that gave regional metastases and those that did not, this thesis brought new knowledge about protein expression and the potential pathophysiological role of differentially expressed proteins in papillary thyroid microcarcinomas and laid the foundations for future research.
Keywords
Proteomika
Štitnjača
Papilarni mikrokarcinom štitnjače
Karcinom
papilarni
Metiltransferaze
Keywords (english)
Proteomics
Thyroid Gland
Papillary Thyroid Microcarcinoma
Carcinoma
Papillary
Methyltransferases
Language croatian URN:NBN urn:nbn:hr:105:700992 Study programme Title: Biomedicine and Health Sciences Type of resource Text Extent 98 str. File origin Born digital Access conditions Open access Terms of use Created on 2023-03-09 09:38:37
