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

• Published in: Cellular physiology and biochemistry Vol. 46; no. 4; pp. 1716 - 1726
• Main Authors: Tao, Yifeng, Li, Hui, Huang, Rongyong, Mo, Dan, Zeng, Tian, Fang, Min, Li, Meiqin
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: AC133 Antigen - genetics; AC133 Antigen - metabolism; Aldh1; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; CD117; CD133; CD44; Chemotherapy; Databases, Factual; Dehydrogenases; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Gene expression; Gynecology; Humans; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Isoenzymes - genetics; Isoenzymes - metabolism; Kinases; Medical prognosis; Meta-analysis; Neoplastic Stem Cells - metabolism; Odds Ratio; Original Paper; Ovarian cancer; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Prognosis; Proportional Hazards Models; Proteins; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Retinal Dehydrogenase - genetics; Retinal Dehydrogenase - metabolism; Signal transduction; Stem cells; Survival Rate; Tumors; CD117; Aldh1; CD44; CD133; Ovarian cancer; Meta-analysis
• DOI: 10.1159/000489586
• ISSN: 1015-8987; 1421-9778

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.