Izražanje PAX8, SOX2 in CD133 v metastazah in okoliškem tkivu pri raku jajčnikov

Sotlar, Špela (author), Breznik Vittori, Barbara (mentor)

Rak jajčnikov je ena izmed najnevarnejših ginekoloških rakavih obolenj, ki zaradi pozne diagnoze in pogostih ponovitev ostaja vodilni vzrok smrti pri pacientkah z raki ženskega reproduktivnega sistema. Ključno vlogo pri odpornosti na zdravljenje in ponovnemu izbruhu bolezni imajo rakave matične celice. Te predstavljajo majhno populacijo tumorskih celic, ki so sposobne samoobnavljanja, plastičnosti in imajo potencial za metastaziranje. Med kirurškim zdravljenjem se običajno odstrani le makroskopsko vidno tumorsko tkivo, lokalizirano na površini peritoneja. Zaradi visoke incidence ponovitve bolezni smo v tej raziskavi usmerili pozornost na peritonealna področja, v katerim makroskopsko ni vidnega tumorja in med operativnim posegom praviloma ostanejo neodstranjena. V sklopu magistrske naloge nas je zanimalo, ali lahko po končanem zdravljenju v tkivu, oddaljenim od makroskopsko vidnih metastaz, zaznamo rakave matične celice, ki lahko predstavljajo mesta za ponovni izbruh bolezni. Analizirali smo izražanje bioloških označevalcev PAX8 (označevalec celic raka jajčnikov), SOX2 (transkripcijski dejavnik pluripotentnosti, povezan s odpornostjo na zdravljenje, ki je prisoten v rakavih matičnih celicah) in CD133 (površinski označevalec rakavih matičnih celic) v metastazah in okoliškem tkivu pri raku jajčnikov. V raziskavo je bilo vključenih deset bolnic, ki so imele diagnosticiran serozni rak jajčnikov visoke ali nizke stopnje. Za analizo izražanja označevalcev v tkivnih biopsijah smo uporabili fluorescenčno imunohistokemijo, kjer smo uporabili fluorescenčno označena protitelesa za zaznavanje specifičnih antigenov. Izvedli smo kvalitativno in kvantitativno analizo izražanja označevalcev PAX8, SOX2 in CD133 in tako določili deleže rakavih matičnih celic v metastazah in okoliških biopsijah. Z rezultati imunofluorescenčne analize smo pokazali, da so po zaključenem zdravljenju tako v metastazah kot v okoliških biopsijah prisotne rakave matične celice. Delež rakavih matičnih celic, ki izražajo tako PAX8 kot SOX2, je v okoliškem tkivu višji kot v metastazah. V okoliškem tkivu smo zaznali prisotnost mikro in malih niš, kjer smo potrdili prisotnost SOX2+ rakavih celic. Ker kirurški posegi običajno ne vključujejo odstranitve okoliškega tkiva, lahko terapevtsko odporne tumorske celice na teh mestih predstavljajo potencialna žarišča za ponovitev bolezni. Rakave matične celice tako predstavljajo ključno novo tarčo za razvoj inovativnih terapevtskih pristopov.

• Language: Slovenian
• Keywords: rak jajčnikov, metastaze, tumor, rakave matične celice, SOX2, PAX8, CD133
• Work type: Master's thesis/paper
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2026
• PID: 20.500.12556/RUL-184536
• Publication date in RUL: 09.07.2026

Secondary language

• Language: English
• Title: Expression of PAX8, SOX2 and CD133 in metastasis and distant tissue in ovarian cancer

Abstract

Ovarian cancer is one of the most dangerous gynaecological malignancies, which, due to late diagnosis and frequent recurrences, remains the leading cause of death among cancers of the female reproductive system. Cancer stem cells play a key role in treatment resistance and disease relapse. These cells represent a small population of tuour cells capable of self-renewal, plasticity, and possessing the potential for metastasis. During surgical treatment only macroscopically visible tumour tissue is removed, localised on the surface of the peritoneum. Due to the high incidence of disease recurrence, we focused our research on peritoneal sites, that usually remain intact during surgery. We were interested in determining whether cancer stem cells were present in tissues distant from metastatic sites, which could potentially serve as sites of recurrence. In this thesis, we investigated the role of the markers PAX8 (marker of ovarian cancer cells), SOX2 (pluripotency transcription factor, related to therapy resistance), and CD133 (surface marker of stem cells, indicator of tumour initiation potential) in metastasis and distant tissue in ovarian cancer. The study included ten patients diagnosed with high- or low-grade serous ovarian carcinoma. We focused on determining whether cancer stem cells persist in tissue after completed treatment and could represent a source for disease recurrence. We used immunohistochemistry to stain tissue sections obtained from the ten patients following therapy. Tissue samples were collected from peritoneal metastases as well as from distant anatomical locations that are typically not removed during surgery. To determine marker expression, we used fluorescent immunohistochemistry. We performed qualitative and quantitative analysis to determine the proportions of cancer stem cells in metastasis and distant tissue. Immunohistochemical analysis revealed that cancer stem cells persist both in metastasis and in distant tumour tissue even after completed treatment. Moreover, the proportion of cancer stem cells in distant tissue was typically higher than in the metastasis themselves. We identified a subset of small and micro niches which contained SOX2+ ovarian cancer stem cells. Because this distant tumour tissue is typically not surgically removed, these cells may represent sites of initiation for disease recurrence. Cancer stem cells could thus represent an important new target for the development of future therapies.

• Keywords: ovarian cancer, metastasis, cancer stem cell, tumour, SOX2, PAX8, CD133