Določanje izražanja prenašalca ATP7B v tkivu bolnic z rakom jajčnikov in kemorezistenca na karboplatin

Bervar, Amber (author), Černe, Katarina (mentor)

Med ginekološkimi raki ima rak jajčnikov najvišjo umrljivost. Med vzroke za visoko umrljivost sodijo nespecifičnost simptomov in posledično odkrivanje bolezni v poznih stadijih ter razvoj kemorezistence na karboplatin, kar ovira zdravljenje. Večina bolnic z rakom jajčnikov bo tekom zdravljenja razvila kemorezistenco na karboplatin, pričakovana življenjska doba bolnic, ki se na sistemsko zdravljenje ne odzivajo, pa je zgolj eno leto. Odkritje označevalca, ki bi pripomogel k zgodnjemu diagnosticiranju raka jajčnikov in/ali bi bil povezan z razvojem kemorezistence na karboplatin, bi močno pripomoglo k izboljšanju zdravljenja te bolezni. Vlogo pri kemorezistenci na karboplatin naj bi v rakavih celicah imela poleg drugih dejavnikov tudi prenašalca bakrovih ionov ATP7A in ATP7B, zato bi lahko bila potencialna označevalca za razvoj kemorezistence pri bolnicah z rakom jajčnikov. Pretekle raziskave so pokazale, da so substrat ATP7A in ATP7B lahko tudi ioni platine oz. kemoterapevtiki na osnovi platine, kot je karboplatin. Oba prenašalca naj bi sodelovala pri izločanju karboplatina iz rakavih celic, zato bi njuno povišano izražanje v rakavih celicah lahko nakazovalo na razvoj kemorezistence. V diplomskem delu smo s kvantitativno verižno reakcijo s polimerazo (qPCR) spremljali, kako se je zapis za ATP7B izražal v tkivu bolnic s seroznim karcinomom visokega gradusa (HGSC), ki zajema rak jajčnikov, rak jajcevodov in primarni peritonealni serozni rak, ter v kemorezistentni celični liniji, ki predstavlja model za HGSC, in v površinskem epiteliju zdravega jajčnika. V slednjih smo ovrednotili prisotnost ATP7B tudi s pretočno citometrijo. Ugotovili smo, da se je več zapisa za ATP7B izražalo v tkivu, odvzetem po predooperativni kemoterapiji, in da je bilo več ATP7B prisotnega v kemorezistentni celični liniji kot v površinskem epiteliju zdravega jajčnika. Rezultati nakazujejo na potencial ATP7B kot označevalca za razvoj kemorezistence pri HGSC.

• Language: Slovenian
• Keywords: rak jajčnikov, HGSC, kemorezistenca, ATP7B
• Work type: Bachelor thesis/paper
• Typology: 2.11 - Undergraduate Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2025
• PID: 20.500.12556/RUL-172525
• COBISS.SI-ID: 255200259
• Publication date in RUL: 08.09.2025

Secondary language

• Language: English
• Title: Determination of ATP7B transporter expression in ovarian cancer patients and carboplatin chemoresistance

Abstract

Ovarian cancer has the highest mortality among gynaecological cancers due to non-specific symptoms that lead to delayed diagnosis and carboplatin chemoresistance, which presents a major setback for successful treatment. During treatment, most patients will develop chemoresistance while those who fail to respond to it die in a year. Therefore, an early-detection biomarker as well as chemoresistance biomarker would benefit the development of treatment for this disease greatly. The development of carboplatin chemoresistance can be assigned to copper efflux transporters ATP7A and ATP7B. Subsequently, they present potential biomarkers for chemoresistance in ovarian cancer patients. Previous research suggests that platinum ions and platinum-based medicines such as carboplatin can act as substrates for ATP7A and ATP7B. Both transporters are thought to play a role in secretion of carboplatin from cancerous cells. Their increased expression could be connected to the development of chemoresistance. Our research was conducted using quantitative polymerase chain reaction (qPCR) for the determination of the expression levels of ATP7B in cancerous tissue of patients with high-grade serous carcinoma (HGSC) including patients diagnosed with ovarian, fallopian tube and peritoneal cancer, and in chemoresistant HGSC-like cell line as well as in healthy ovarian surface epithelium. Levels of ATP7B were also measured with flow cytometry in the last two. We determined that the expression of ATP7B was higher in tissues samples sampled after neoadjuvant chemotherapy was administered. We also determined that the levels of ATP7B were higher in chemoresistant cell-line than in healthy ovarian surface epithelium. We concluded that the results align with a potential role of ATP7B as a biomarker for the development of chemoresistance in HGSC.

• Keywords: ovarian cancer, HGSC, chemoresistance, ATP7B