Pomen epitelijsko-mezenhimskega prehoda pri napredovanju in zasevanju raka debelega črevesa

Pavlič Ločniškar, Ana (author), Zidar, Nina (mentor), Hauptman, Nina (comentor)

V doktorskem delu smo raziskali pomen epitelijsko-mezenhimskega prehoda (EMP) in mezenhimsko-epitelijskega prehoda (MEP) pri napredovanju in zasevanju raka debelega črevesa in danke (RDČD). V prvem delu smo pokazali, da imata EMP in MEP pomembno vlogo pri napredovanju in zasevanju RDČD, vendar ne kot polni EMP/MEP, temveč kot delni EMP/MEP. Dokazali smo, da sta EMP in MEP vpletena v nastanek zasevkov pri limfogenem in hematogenem širjenju tumorja, kljub temu pa označevalci EMP na invazivnem robu pri napredovalem karcinomu ne morejo služiti kot dodaten napovedni dejavnik zasevanja. V drugem delu smo pokazali, da je delni EMP aktiviran na delu invazivnega roba z infiltrativno rastjo, kjer so prisotni tumorsko brstenje in/ali slabo diferencirane skupine, na ekspanzivnem robu pa EMP ni aktiviran. V tretjem delu smo dokazali, da je nabadanje tkivnega bloka z iglo ustrezna tehnika za preučevanje razlik v izražanju označevalcev EMP med osrednjim delom tumorja in invazivnim robom, neustrezna pa za primerjavo med morfološko različnimi predeli vzdolž invazivnega roba. V teh primerih je obvezna uporaba laserske mikrodisekcije. V zadnjem delu smo z bioinformatskimi orodji odkrili dolge nekodirajoče RNA, ki bi lahko bile vpletene v regulacijo EMP v RDČD.

• Language: Slovenian
• Keywords: delni EMP, kolorektalni karcinom, laserska mikrodisekcija, mikro RNA, zasevanje
• Work type: Doctoral dissertation
• Organization: MF - Faculty of Medicine
• Year: 2024
• PID: 20.500.12556/RUL-153520
• Publication date in RUL: 12.01.2024

Secondary language

• Language: English
• Title: Role of epithelial-mesenchymal transition in colon cancer progression and metastasis

Abstract

In this doctoral thesis we investigated the role of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) in colorectal cancer (CRC) progression and metastasis. Firstly, we showed that EMT and MET play an important role in the progression and metastasis of CRC, but not as full EMT/MET, but as partial EMT/MET. We demonstrated that EMT and MET are involved in both lymphogenic and hematogenous tumor spread. Additionaly, we showed that EMT markers at the invasive front of advanced CRC cannot serve as additional predictive factors of metastasis. Secondly, we demonstrated that partial EMT is activated at the invasive front of CRC exhibiting an infiltrative growth, where tumor budding and/or poorly differentiated clusters are present, while EMT is not activated at the invasive front exhibiting an expansive growth. Thirdly, we demonstrated that punching tissue block is a adequate technique for studying the differences in tumor gene expression between the central part and the invasive front of CRC, but is insufficient to analyze and compare morphologically distinct patterns along the invasive front, including tumor budding. For this purpose, the use of laser capture microdissecton is essential. Lastly, we used bioinformatics analysis to identify long non-coding RNAs that could be involved in regulation of EMT in CRC.

• Keywords: partial EMT, colorectal cancer, laser capture microdissection, micro RNA, metastasis