Timidin kinaza 1 kot diagnostični tumorski označevalec pri bolnicah z rakom jajčnikov

Cviič, Diana (author), Osredkar, Joško (mentor)

Rak jajčnikov predstavlja enega izmed zahrbtnih in agresivnih oblik raka. Zaradi asimptomatskih simptomov se rak jajčnikov običajno diagnosticira v poznih stadijih (FIGO stadij III ali IV), ko operacija in kemoterapija nista zelo učinkoviti. Za odkrivanje raka jajčnikov trenutno ni učinkovitega presejalnega programa in primernih presejalnih metod. V naši raziskavi smo analizirali diagnostično vlogo koncentracije TK1, aktivnosti TK1, tumorskega označevalca CA 125 in HE4 ter algoritma ROMA za zgodnje odkrivanje raka jajčnikov pri ženskah v predmenopavzi in pomenopavzi v primerjavi s kontrolno skupino. Poleg tega smo prvi ovrednotili tudi vlogo TK1 specifične aktivnosti (TK1 SA), ki temelji na razmerju med TK1a ter TK1p in tudi v kombinaciji s tumorskima označevalcema CA 125 in HE4 ter algoritmom ROMA. Na Kliničnem oddelku za ginekologijo v Ljubljani in na Zavodu RS za transfuzijsko medicino je bilo odvzetih 198 vzorcev, med katerimi so bile bolnice z mejno malignim tumorjem jajčnikov in rakom jajčnikov (N = 62), z benignim tumorjem (N = 72) in zdrave ženske kot kontrolna skupina (N = 64). Preveriti smo želeli tri hipoteze, in sicer: 1. Koncentracija encima TK1, aktivnost encima TK1 in njuno razmerje je višje pri bolnicah z rakom jajčnikov v primerjavi z benignim tumorjem in s kontrolno skupino ter bo naraščala glede na stadij bolezni. 2. Povišane vrednosti koncentracije encima TK1 in aktivnosti encima TK1 so povezane z agresivnostjo oziroma prognozo bolezni. 3. Dodatek koncentracije oziroma aktivnosti encima TK1 v algoritem ROMA izboljša specifičnost in občutljivost za detekcijo raka jajčnika. Hipotezo 1 in 2 smo deloma potrdili, hipotezo 3 pa smo v celoti potrdili. Do zdaj še ni bilo objavljene raziskave, ki bi uporabila kombinacijo koncentracije encima TK1 in aktivnosti encima TK1 pri diagnozi raka jajčnikov. Na splošno ti rezultati kažejo, da bi lahko razmerje encima TK1 SA dopolnjeval tumorska označevalca CA 125 ali HE4 pri odkrivanju zgodnjega stadija raka jajčnikov.

• Language: Slovenian
• Keywords: rak jajčnikov, CA 125, HE4, indeks ROMA, timidin kinaza 1, koncentracija encima TK1, aktivnost encima TK1, TK1 SA
• Work type: Doctoral dissertation
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-152872
• Publication date in RUL: 10.12.2023

Secondary language

• Language: English
• Title: Thymidine kinase 1 as a diagnostic tumor marker in patients with ovarian cancer

Abstract

Ovarian cancer is one of the most insidious and aggressive forms of cancer. Due to asymptomatic symptoms, ovarian cancer is usually diagnosed in late stages (FIGO stage III or IV), when surgery and chemotherapy are not very effective. There is currently no effective screening program or suitable screening methods for ovarian cancer detection. In our study, we analyzed the diagnostic role of TK1 concentration, TK1 activity, CA 125, HE4, and ROMA index for the early detection of ovarian cancer in premenopausal and postmenopausal women compared to the control group. In addition, we also evaluated the role of TK1 specific activity (TK1 SA) based on the ratio between TK1a and TK1c for the early diagnosis of ovarian cancer and also in combination with traditional tumor markers such as CA 125, HE4, and ROMA index. At the Clinical Department of Gynecology in Ljubljana and at the Institute of Transfusion Medicine of the Republic of Slovenia, 198 samples were taken, among which were patients with borderline malignant ovarian tumors and ovarian cancer (N = 62), with benign tumors (N = 72) and healthy women as a control group (N = 64). We intended to test three hypotheses: 1. The TK1 concentration, TK1 activity, and their ratio are higher in patients with ovarian cancer compared to the benign tumor and the control group and will increase according to the stage of the disease. 2. Increased values of TK1 concentration and TK1 activity are associated with aggressiveness or disease prognosis. 3. The addition of TK1 concentration or TK1 activity to the ROMA index improved the specificity and sensitivity for the detection of ovarian cancer. Hypotheses 1 and 2 were partially confirmed, while hypothesis 3 was fully confirmed. Until now, there has been no published research using the combination of TK1 enzyme concentration and TK1 enzyme activity in the diagnosis of ovarian cancer. Overall, these results suggest that the TK1 SA enzyme ratio could complement the tumor markers CA 125 or HE4 in the detection of early stage ovarian cancer.

• Keywords: ovarian cancer, CA 125, HE4, ROMA index, thymidine kinase 1, TK1 protein, TK1 activity, TK1 SA