Disertasi

Pengaruh Ekspresi CD117, CD133, CD24, CD44, ALDH terhadap Progression Free Survival Pasien Kanker Ovarium Epitel Stadium Lanjut = The Influence of CD117, CD133, CD24, CD44, and ALDH Expression on Progression-Free Survival in Advanced-Stage Epithelial Ovarian Cancer Patients.

Penanda sel punca kanker (SPK) semakin diakui sebagai indikator penting terhadap agresivitas tumor, resistensi terhadap kemoterapi, dan kekambuhan pada kanker ovarium tipe epitel. Penelitian ini mengevaluasi ekspresi penanda SPK, khususnya CD117, CD133, CD24, CD44, dan ALDH, baik secara individual maupun dalam kombinasi, terhadap progresi bebas kanker progression free survival (PFS) dua tahun pada pasien kanker ovarium tipe epitel stadium lanjut. Sebanyak 117 pasien kanker ovarium epitel stadium lanjut dianalisis dalam sebuah kohort ambispektif. Kekambuhan dievaluasi menggunakan kriteria Response Evaluation Criteria in Solid Tumours (RECIST). Ekspresi penanda SPK diukur menggunakan imunohistokimia dan dikategorikan berdasarkan nilai cut-off H-score yang diperoleh dari analisis kurva Receiver Operating Characteristic (ROC). Hubungan antara penanda dengan kekambuhan dan PFS dianalisis menggunakan uji Chisquare, Kaplan–Meier, dan regresi Cox. Analisis jalur digunakan untuk mengevaluasi potensi interaksi langsung maupun tidak langsung antar-penanda. Kekambuhan terjadi pada 65,8% pasien dua tahun setelah terapi, terutama pada stadium III–IV. Penanda SPK individual menunjukkan kemampuan diskriminatif yang rendah (AUC < 0,6), dan sebagian besar penanda dengan ekspresi tinggi memperlihatkan kecenderungan terhadap PFS yang lebih pendek serta peningkatan risiko kekambuhan. Panel lima penanda secara bersamaan serta kombinasi CD133– ALDH merupakan prediktor kekambuhan yang bermakna. Analisis Structural Equation Modelling (SEM) menunjukkan adanya interaksi tidak langsung yang bermakna dalam jalur SPK yang berkontribusi terhadap risiko kekambuhan. Simpulan: Meskipun penanda SPK individual menunjukkan nilai prognostik independen yang terbatas, ekspresi gabungan beberapa penanda memberikan stratifikasi risiko yang lebih baik terhadap kekambuhan dan kelangsungan hidup pada kanker ovarium epitel stadium lanjut. Profil SPK kombinasi berpotensi meningkatkan kemampuan prediksi serta membantu dalam penentuan strategi surveilans dan terapi yang lebih personal.
Kata kunci: ALDH, CD24, CD44, CD117, CD133, kanker ovarium tipe epitel, progresi bebas kanker, sel punca kanker


Cancer stem cell (CSC) markers are increasingly recognized as key indicators for tumour aggressiveness, chemoresistance and recurrence in epithelial ovarian cancer (EOC). The aim this study is to evaluate the expression of CSC markers, specifically CD117, CD133, CD24, CD44, and ALDH, individually and in combination, on two-year progression-free survival (PFS) in patients with advanced-stage EOC. An ambispective cohort of 117 advanced-EOC patients was analysed. Recurrence was assessed using Response Evaluation Criteria in Solid Tumours (RECIST) criteria. CSC marker expression was measured by immunohistochemistry and categorised using H-score cut-offs derived from Receiver operating characteristic (ROC) analysis. Associations with recurrence and PFS were examined using Chi-square, Kaplan–Meier, and Cox regression. Path analysis evaluated potential direct and indirect interactions among markers. Twoyear recurrence occurred in 65.8% of patients, predominantly in stage III–IV disease. Individual CSC markers demonstrated poor discriminative ability (AUC < 0.6), and most high-expression markers showed a trend toward shorter PFS and higher recurrence risk. Low CD133 expression was associated with longer PFS (12.0 vs 10.0 months; p = 0.045). The combined five-marker panel and the CD133– ALDH signature were significant predictors of recurrence. Patients with low mean expression had longer PFS (17.94 vs 13.85 months, p = 0.011; 17.0 vs 14.72 months, p = 0.034). Although no markers remained significant in the multivariate analysis, the Structural Equation Modelling (SEM) analysis revealed significant indirect interactions within CSC pathways that contributed to the risk of recurrence. Conclusion: While individual CSC markers showed limited independent prognostic value, their combined expression provided superior risk stratification for recurrence and survival in advanced EOC. Multimarker CSC profiling may enhance prognostication and aid in guiding personalized surveillance and therapeutic strategies.
Keywords: ALDH, CD24, CD44, CD117, CD133, Cancer Stem Cells, Epithelial ovarian cancer, Progression-free survival.