Epithelial ovarian cancer with CD117 phenotype is highly aggressive and resistant to chemotherapy

Conic, Irena; Stanojevic, Zorica; Veličković, Ljubinka Janković; Stojnev, Slavica; Ristic-Petrovic, Ana; Miljan, Krstic; Stanojević, Milenko; Bogdanović, Dragan; Stefanović, Vladisav

doi:10.1111/jog.12758

Cited by 20 publications

(17 citation statements)

References 19 publications

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“…A similar result was observed in another meta-analysis enrolling 2,161 EOC patients, which demonstrated CD44 expression was positively correlated with TNM stage and 5-year OS rate 28. With regard to CD117, to the best of our knowledge, no comprehensive evidence-based analysis is currently available to evaluate its clinical significance in EOC patients, although controversial correlations with clinical outcomes have been found in several recent studies 19,22. Therefore, it is necessary to perform a meta-analysis to identify whether CD117 can serve as a predictive biomarker for the clinical management of EOC patients.…”

Section: Discussionsupporting

confidence: 75%

“…The characteristics of these seven papers are summarized in Table 1 19,21–26. A total of 1,247 EOC patients from seven countries (Germany, Norway, Serbia, Finland, Austria, Canada, and the USA) were enrolled in our meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…Some studies have indicated that CD117 is an adverse prognostic factor, while other studies found that CD117 expression is unrelated to clinical outcome or may even serve as a favorable prognostic factor 19–22. Thus, it is essential to make a comprehensive and objective evaluation of its clinical significance for EOC patients.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of the cancer stem cell marker CD117 predicts poor prognosis in epithelial ovarian cancer patients: evidence from meta-analysis

Yang¹,

Yan²,

Liu³

et al. 2017

OTT

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05-3.26). EOC patients with high CD117 expression had significantly worse OS (hazard ratio [HR] =1.39, 95% CI =1.03-1.90) than patients with low CD117 expression. However, no significant correlation was found between CD117 expression and disease-free survival (HR =1.31, 95% CI =0.79-2.17). In subgroup analysis, CD117 was identified as a significant prognostic factor for overall survival in European patients (HR =1.59, 95% CI =1.13-2.23), younger patients (,60 years) (HR =1.59, 95% CI =1.10-2.30), studies with sample sizes 200 (HR =1.84, 95% CI =1.32-2.56), and the mixed histological types (HR =1.47; 95% CI =1.08-2.00). Conclusion: Our meta-analysis suggests that CD117 is associated with EOC progression and can serve as a promising prognostic predictor for EOC patients. However, larger scale multicenter clinical trials are still needed to further validate our results.

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Section: Discussionsupporting

confidence: 75%

Section: Resultsmentioning

confidence: 99%

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Overexpression of the cancer stem cell marker CD117 predicts poor prognosis in epithelial ovarian cancer patients: evidence from meta-analysis

Yang¹,

Yan²,

Liu³

et al. 2017

OTT

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“…It is normally phosphorylated and activated by binding to the KIT ligand, which is also called stem cell factor [153]. It is a widely used stemness marker for recognizing cancer stem cells in various tumour types, including ovarian cancer [154–156], endometrial cancer and osteosarcoma [155, 157, 158]. In HPV-associated cervical cancer, SCF-activated c-Kit may activate interleukin-2 receptor betagamma signalling in the absence of IL-2, promoting T cell proliferation [159].…”

Section: C-kitmentioning

confidence: 99%

Cancer stem cells (CSCs), cervical CSCs and targeted therapies

2016

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Accumulating evidence has shown that cancer stem cells (CSCs) have a tumour-initiating capacity and play crucial roles in tumour metastasis, relapse and chemo/radio-resistance. As tumour propagation initiators, CSCs are considered to be promising targets for obtaining a better therapeutic outcome. Cervical carcinoma is the most common gynaecological malignancy and has a high cancer mortality rate among females. As a result, the investigation of cervical cancer stem cells (CCSCs) is of great value. However, the numbers of cancer cells and corresponding CSCs in malignancy are dynamically balanced, and CSCs may reside in the CSC niche, about which little is known to date. Therefore, due to their complicated molecular phenotypes and biological behaviours, it remains challenging to obtain “purified” CSCs and continuously culture CSCs for further in vitro studies without the cells losing their stem properties. At present, CSC-related markers and functional assays are used to purify, identify and therapeutically target CSCs both in vitro and in vivo. Nevertheless, CSC-related markers are not universal to all tumour types, although some markers may be valid in multiple tumour types. Additionally, functional identifications based on CSC-specific properties are usually limited in in vivo studies. Furthermore, an optimal method for identifying potential CCSCs in CCSC studies has not been previously published, and these techniques are currently of great importance. This article updates our knowledge on CSCs and CCSCs, reviews potential stem cell markers and functional assays for identifying CCSCs, and describes the potential of targeting CCSCs in the treatment of cervical carcinoma.

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“…The sample sizes of the included studies ranged from 11 to 440. Among these studies, 15 studies involved patients with ALDH1 [19, 22, 26, 30-41], 8 studies involved patients with CD133 [18, 23, 25, 30, 31, 37, 42, 43], 25 studies involved patients with CD44 [17, 21, 24, 44-64, 66], 7 studies involved patients with CD117 [13, 20, 26, 27, 67-69], 3 studies involved patients with ALDH1 and CD133 [30, 31, 37], and 1 study involved patients with ALDH1 and CD117 [26]. According to the NOS quality assessment, 52 of the studies were categorized as high quality.…”

Section: Resultsmentioning

confidence: 99%

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

Tao

Huang

et al. 2018

Cell Physiol Biochem

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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.

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Epithelial ovarian cancer with CD117 phenotype is highly aggressive and resistant to chemotherapy

Abstract: Residual tumors and chemotherapy treatment were more frequent in patients with positive CD117 expression. The outcome was dependent on the type of OC; a worse outcome, including a shorter survival, was documented in the mucinous and endometrioid OC cases.

Cited by 20 publications

References 19 publications

Overexpression of the cancer stem cell marker CD117 predicts poor prognosis in epithelial ovarian cancer patients: evidence from meta-analysis

Overexpression of the cancer stem cell marker CD117 predicts poor prognosis in epithelial ovarian cancer patients: evidence from meta-analysis

Cancer stem cells (CSCs), cervical CSCs and targeted therapies

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

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