Imunohistokemijska izraženost BORIS i MAGE-A10 u metastazirajućim i nemetastazirajućim kolorektalnim karcinomima

doctoral thesis

• Title (english): Immunohistochemical expression of BORIS and MAGE-A10 in metastatic and nonmetastatic colorectal cancer
• Author: Vedran Tomašić
• Mentor: Monika Ulamec (mentor)
• Committee member: Davor Tomas (predsjednik povjerenstva)
• Committee member: Borislav Belev (član povjerenstva)
• Committee member: Davor Hrabar (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2021-04-29, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Rak debelog crijeva (engl. colorectal cancer, CRC) je rastući problem u zapadnim
zemljama. Identifikacija novih biomarkera mogla bi poboljšati ranu dijagnostiku i uvesti
ciljanu terapiju kao ključ boljeg preživljenja. Proteini BORIS i MAGE-A10 pripadaju
skupini cancer-testis antigena (CTA). Oba proteina imaju ključnu ulogu tijekom rane
embriogeneze dok u odraslom tkivu nisu izraženi. CTA proteini su detektirani i u različitim
vrstama tumora, uključujući i CRC, čime kao potencijalni biomarkeri mogu biti cilj
imunoterapije. Stoga smo proveli istraživanje na 50 uzoraka nemetastatskih i 45 uzoraka
metastatskih CRC i pripadajućim jetrenim metastazama te smo metodom
imunohistokemijskog bojenja u stanicama karcinoma i okolnoj stromi odredili izraženost
proteina BORIS i MAGE-A10. Neparametrijskim testom korelacija analizirali smo
korelacije izraženosti oba proteina s patohistološkim i biokemijskim karakteristikama CRC,
uz granicu statističke značajnosti nižu od 0,05. Naši rezultati pokazuju izraženost BORIS u
više od 90% svih uzoraka CRC, dok je MAGE-A10 izražen u 27,5%. MAGE-A10 je
značajno jače izražen u jetrenim metastazama (52,5%). Slabija izraženost BORIS u
tumorskim stanicama korelira s višim gradusom tumora (P=0.035), dok izraženost u jetrenim
metastazama korelira s gradusom (P=0,002) i perivaskularnom invazijom (P=0,033). Jača
izraženost MAGE-A10 značajno korelira s perineuralnom infiltracijom (P=0,031), M
stadijem bolesti (P=0,037) i ženskim spolom (P=0,014). Možemo zaključiti da jaka
izraženost BORIS u CRC kao i značajno jača izraženost MAGE-A10 u metastatskim
lezijama kolorektalnog karcinoma mogu poslužiti za razvoj personaliziranih strategija
pristupa prognozi, korištenja ciljane imunoterapije kao i razvoja cjepiva protiv raka.

Abstract (english)

Identification of novel biomarkers for early detection, prognosis and targeted therapy could
lead to better survival of colorectal cancer (CRC). BORIS and MAGE-A10 are cancer-testis
antigens (CTA) which play a key role during early embryogenesis without expression in
adult tissue. CTA are also expressed in various human cancers, including CRC, making them
potential target for cancer immunotherapy. A study has been conducted on 50 nonmetastatic,
and 45 metastatic CRC with liver metastases. BORIS and MAGE-A10 protein
expression were determined by immunohistochemical staining and associated with the
pathohistological and biochemical characteristics of CRC using a nonparametric correlation
assay, with P=.05. BORIS was expressed in more than 90% of all CRC samples. Weaker
expression of BORIS correlates with higher tumor grade (P=.035), while in liver metastases
it correlates with grade (P=.002) and perivascular invasion (P=.033). MAGE-A10 is
expressed in 27.5% of CRC, and is significantly more pronounced in liver metastases
(52.5%). Stronger expression of MAGE-A10 correlates with perineural infiltration (P=.031),
M stage of the disease (P=.037) and female gender (P=.014). In conclusion strong expression
of BORIS in CRC and MAGE-A10 in CRC liver metastases may serve as development tools
for new treatment approaches such as targeted immunotherapy or cancer vaccine.

• Keywords: kolorektalni karcinom; cancer-testis antigeni; tumorska stroma; BORIS; MAGE-A10; imunoterapija; cjepivo protiv kolorektalnog karcinoma
• Keywords (english): colorectal cancer; cancer-testis antigens; BORIS; MAGE-A10; biomarker; immunotherapy; colorectal cancer vaccine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:244666
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 120 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-06-25 08:10:02