Disertasi

Ekspresi CD44 + /CD24 - , RAD6 dan DDB2 pada Cancer Stem Cells (CSCs) di Kanker Ovarium Sebagai Prediktor Respons Terapi. = The Expression of CD44 + /CD24 - , RAD6 and DDB2 in Cancer Stem Cells (CSCs) of Ovarian Cancer as Chemotherapy Response Predictors.

Kanker ovarium merupakan kanker paling mematikan ke-8 pada perempuan di dunia. Pasien kanker ovarium umumnya akan mengalami kemoresistensi, kekambuhan dan prognosis buruk setelah operasi sitoreduktif dan kemoterapi berbasis platinum. Hal tersebut berhubungan dengan peningkatan ekspresi Cancer Stem Cells (CSCs) CD44 + /CD24 - , RAD6, dan penurunan DDB2. Penelitian ini bertujuan untuk menganalisis hubungan ekspresi CSCs, RAD6 dan DDB2 dengan kemoresistensi kanker ovarium di jaringan kanker ovarium dan sirkulasi darah. Penelitian kohort ambispektif ini dilakukan di RSUP Cipto Mangunkusumo, RSUD Tarakan, RSUP Dharmais, dan RSUP Fatmawati pada Februari 2018–Februari 2022. Subjek adalah 64 orang pasien yang dibagi menjadi dua kelompok. Semua subjek menjalani operasi sitoreduktif dan pemeriksaan histopatologi. Kemoterapi diberikan sebanyak enam seri diikuti enam bulan observasi, kemudian ditentukan respons terapi dengan kriteria Response Criteria in Solid Tumors (RECIST). Uji imunohistokimia dilakukan langsung ke jaringan kanker ovarium (retrospektif) dan uji flowsitometri darah (prospektif) untuk menilai Ekspresi CSCs, RAD6 dan DDB2. Terdapat peningkatan Ekspresi CSCs, RAD6 serta penurunan bermakna ekspresi DDB2 (p < 0,05) di jaringan kanker ovarium kemoresisten, dan peningkatan bermakna Ekspresi CSCs, dan RAD6 yang bermakna (p < 0,05) di sirkulasi darah penderita kanker ovarium. Ekspresi DDB2 di uji imunohistokimia adalah protein dengan nilai AUC terbaik sedangkan di uji flowsitometri, CSCs memiliki nilai AUC terbaik. Disusun skor IHC-UNEDO (imunohistokimia) dan skor FCMUNEDO (flowsitometri) untuk membantu memprediksi respons terapi. Penelitian ini menunjukkan bahwa terdapat peningkatan Ekspresi CSCs, RAD6 dan penurunan DDB2 di jaringan kanker ovarium, serta peningkatan Ekspresi CSCs di sirkulasi darah penderita kanker ovarium dan protein tersebut merupakan prediktor respons terapi kanker ovarium yang baik.
Kata Kunci: CD44 + /CD24 - ; DDB2; Kanker Ovarium; Kemoresistensi; RAD6.


Ovarian cancer is the 8 th deadliest women cancer around the world. Almost all ovarian cancer patients would experience chemoresistance, recurrence, and poor prognosis after cytoreductive surgery and platinum-based chemotherapy. It is caused by the expression of Cancer Stem Cells (CSCs) CD44 + /CD24 - , RAD6, and DDB2. This study objective is to analyze the correlation between the expression of CSCs, RAD6 and DDB2 in ovarian cancer tissue and blood circulation with ovarian cancer chemoresistance This ambispective cohort study conducted at of the Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital in Februari 2018 untill Februari 2022. The subjects were 64 patients divided into two groups. All subjects underwent cytoreductive debulking and histopathological examination followed by six series of chemotherapy and six months of observation. We determined the therapy’s response with the Response Criteria in Solid Tumors (RECIST). We performed immunohistochemistry tests to ovarian cancer tissue (retrospective) and flowcytometry blood tests (prospective) to examine the expression of CSCs, RAD6 and DDB2. We found significant relationship between increased levels of CSCs, RAD6 and reduced levels of DDB2 (p < 0,05) in chemoresistant ovarian cancer tissue. Flowcytometry test also found a significant relationship between increased levels of CSCs, and RAD6 (p < 0,05) in blood circulation. DDB2 has the best immunohistochemistry AUC value while CSCs was the best in flowcytometry. The IHC-UNEDO scores and FCM-UNEDO scores were arranged to predict ovarian cancer chemoresistance. These results indicate that there was overexpression of CSCs, RAD6 and low expression of DDB2 in ovarian cancer tissue and overexpression of CSCs in blood circulation and these proteins were good predictors of ovarian cancer chemoresistance.
Keywords: CD44 + /CD24 - ; Chemoresistance; DDB2; Ovarian Cancer; RAD6.