Abstract
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.
Highlights
Cervical cancer is the fourth most common type of gynecological cancer worldwide (Pimple et al, 2016)
We found that high expressions of CD44, Sex determining region Y-box 2 (SOX2), Octamer-binding transcription factor 4 (OCT4), aldehyde dehydrogenase 1 (ALDH1), and Cluster differentiation 49f (CD49f) were associated with poor overall survival (OS)
Overexpression of OCT4, SOX2, and ALDH1 were associated with worse disease-free survival (DFS)
Summary
Cervical cancer is the fourth most common type of gynecological cancer worldwide (Pimple et al, 2016). Most cervical cancer is caused by human papillomavirus (HPV) infection (Hashiguchi et al, 2019). There were 528,000 new cases every year, with 266,000 deaths in 2012 worldwide. Cervical cancer has high mortality rates among women (Pimple et al, 2016). There were 14,480 new cases in the United States in 2021 (American Cancer Society, 2021). ( American Cancer Society, 2021). The 5-year survival rate of cervical cancer for stage IB-IVA was 62.6% (Yoon et al, 2015)
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