Document Type : Systematic Review and Meta-analysis
Fellowship Gynecology Oncology Division, Department of Obstetrics and Gynecology, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Jakarta, Indonesia.
Department of Obstetrics and Gynecology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Dr. Sayidiman Regional Public Hospital, Magetan, East Java, Indonesia.
Gynecology Oncology Division, Department of Obstetrics and Gynecology, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital, Faculty of Medicine, Jakarta, Indonesia.
Objectives: Prognostic biomarkers in cervical cancer are widely investigated, including cancer stem cell (CSC) markers. However, their significance remains uncertain. This study aimed to determine the role of cervical cancer stem cell (CCSC) markers for survival. Materials and Methods: We conducted a systematic review and meta-analysis (PROSPERO CRD42021237072) of studies reporting CCSC markers as the prognostic predictor based on PRISMA guidelines. We included English articles investigating associations of CCSCs expression in tissue tumor with overall survival (OS) or disease-free survival (DFS) from PubMed, EBSCO, and The Cochrane Library databases. The quality of studies was analyzed based on Newcastle-Ottawa Quality Assessment Scale. Results: From 413 publications, after study selection with inclusion and exclusion criteria, 22 studies were included. High expressions of CCSC markers were associated with poor OS and DFS (HR= 1.05, 95% CI: 1.03 – 1.07, P <0.0001; HR= 1.31, 95% CI: 1.09 – 1.17, P <0.00001; respectively). Sub-analysis of individual CCSC markers indicated significant correlations between CD44 (HR= 1.14, 95% CI: 1.07 – 1.22, P 0.0001), SOX2 (HR= 1.58, 95% CI: 1.17 – 2.14, P 0.003), OCT4 (HR= 1.03, 95% CI: 1.01 – 1.06, P 0.008), ALDH1 (HR= 1.36, 95% CI: 1.13 – 1.64, P 0.001), and CD49f (HR= 3.02, 95% CI: 1.37 – 6.64, P 0.006) with worse OS; OCT4 (HR= 1.14, 95% CI 1.06 – 1.22, P 0.0003), SOX2 (HR= 1.11, 95% CI: 1.06 – 1.16, P <0.0001), and ALDH1 (HR= 1.22, 95% CI: 1.10 – 1.35, P 0.0002) with poor DFS. We did not conduct a meta-analysis for MSI-1 and CK17 because only one study investigated those markers. Conclusion: Expressions of OCT4, SOX2, and ALDH1 were associated with poor OS and DFS in cervical cancer tissue. These markers might have potential roles as prognostic biomarkers to predict unfavorable survival.