Clinicopathological and Prognostic Significance of Cancer Stem Cell Markers in Ovarian Cancer Patients: Evidence from 52 Studies

Abstract

Background/Aims: Relevant markers of cancer stem cells (CSCs) may serve as commonly used biomarkers of ovarian cancer (OC). However, their actual clinicopathological and prognostic significance remains inconclusive. Thus, we conducted a meta-analysis to quantitatively evaluate the association between the expression of CSC-relevant markers (ALDH1, CD117, CD133, and CD44) and OC. Methods: We used an odds ratio (OR) and a hazard ratio (HR) with a 95% confidence interval (CI) to estimate the effects by analyzing 52 studies from a literature search. Heterogeneity and sensitivity were evaluated, as well. Publication bias was assessed using funnel plots and Egger tests. Results: ALDH1 expression was statistically associated with FIGO stage (OR=1.872, 95%CI=1.14-3.076, P=0.013) and lymph invasion (OR=2.78, 95%CI=1.08-7.152, P=0.034). CD117 expression was significantly associated with FIGO stage (OR=2.01, 95%CI=1.35-2.98, P=0.001). CD133 expression was correlated with FIGO stage (OR=3.410, 95%CI=2.196-5.294, P< 0.001) and differentiation grade (OR=2.672, 95%CI=1.354-5.272, P=0.005). CD44s was related to chemotherapy resistance (OR=3.218, 95%CI=1.148-9.016, P=0.026). Furthermore, overexpression of ALDH1 (HR=1.494, 95%CI=1.207-1.849, P< 0.001), CD117 (HR=1.395, 95%CI=1.025-1.898, P=0.034) or CD44s (HR=1.725, 95%CI=1.135-2.623, P=0.011) was associated with poor OS. Further, overexpression of both ALDH1 (HR=1.524, 95%CI=1.158-2.007, P=0.003) and CD44s (HR=2.12, 95%CI=1.692-2.657, P< 0.001) was correlated with worse DFS. Conclusion: CSC markers are useful predictive or prognostic biomarkers for OC in clinical assessments. Combined detection of CSC marker expression may be a powerful tool for prognostic predictions in clinical practice for patients with OC.

Novel Therapeutic Strategies for Ovarian Cancer Stem Cells

“…These analyses are currently "gold standard" assays to measure key CSC properties such as self-renewal and multipotency (52). In support of these preclinical findings, clinical significance of CSCs was recently confirmed by a number of studies demonstrated the association of CSC markers with clinicopathological parameters and clinical outcomes of OC patients (69).…”

“…Additionally, radio-and chemotherapy treatments have been shown to enrich CSC subpopulations in residual tumors because of selective pressure on drug-resistant cells (65)(66)(67) and due to tumor cell plasticity (64). Even though the CSC state has high plasticity, it is of high clinical importance as a potential marker for clinical outcome and target for anticancer treatment (68,69).…”

Association between Expression of CD133 and Aldehyde Dehydrogenase 1A1 (ALDH1A1) with FIGO Stage in Serous Ovarian Cancer

“…11 CD133 and ALDH1A1 are CSC marker that can be identified in OC and correlate with stage in OC. 12 CD133 promote cell proliferation, tumorigenesis, tumor invasion and metastasis through induction of NF-κB and upregulation of MMP9. 13 CD133 is also involved in the activation of the PI3K / Akt and Wnt / β Catenin pathways which induce self renewal potential, tumorigenesis and metastasis.…”

“…Ovarian cancer (OC) is an epithelial malignancy of ovary, the seventh most common cancer and the eighth cause of cancerrelated death among women worldwide. 1,2 GLOBOCAN 2012 showed that incidence of OC were 239,000 cases with 152,000 deaths. 2 Incidence of OC is getting higher by year.…”

“…CSC are considered to play an important role in the occurrence of resistance, proliferation, progression and initiation of tumor cell metastasis. 1,9 Identification of CSC in SOC has an important potential in providing optimal management and become predictors in determining aggressiveness and can subsequently become a reference in the development of anti-CSC therapy. 10 There are many CSC markers in SOC: CD24, CD44, CD117, CD133 and aldehyde dehydrogenase isoform 1 (ALDH1).…”