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Meta-Analysis
. 2021 Dec 1;22(12):4057-4065.
doi: 10.31557/APJCP.2021.22.12.4057.

The Prognostic Value of Cancer Stem Cell Markers in Cervical Cancer: A Systematic Review and Meta-Analysis

Moh Nailul Fahmi  1   2 , Inge Nandya Hertapanndika  3 , Fitriyadi Kusuma  4
Affiliations
Meta-Analysis

The Prognostic Value of Cancer Stem Cell Markers in Cervical Cancer: A Systematic Review and Meta-Analysis

Moh Nailul Fahmi et al. Asian Pac J Cancer Prev. .

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.

Keywords: ALDH1; Cervical cancer stem cell marker; Oct4; SOX2; prognostic biomarker.

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Figures

Figure 1
Figure 1
Figure 1. PRISMA Flow Diagram (Moher et al., 2009).
Figure 2
Figure 2
Forest Plot of the Association between Cancer Stem Cell Markers Expression and Overall Survival in Cervical Cancer Patients
Figure 3
Figure 3
Forest Plot of The Correlation between Cancer Stem Cell (CSC) Markers Expression and Disease-Free Survival (DFS) in Cervical Cancer Patients
Figure 4
Figure 4
Funnel Plot to Examine Publication Bias for Overall Survival (OS) and Disease-Free Survival (DFS).
Figure 5
Figure 5
Funnel Plot to Examine Publication Bias of CD44, SOX2, OCT4, ALDH1, and CD49f for Overall Survival (OS).
Figure 6
Figure 6
Funnel plot to examine publication bias of SOX2, OCT4, and ALDH1 for disease-free survival (DFS).
See this image and copyright information in PMC

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