scholarly journals Development and Validation for Prognostic Nomogram of Epithelial Ovarian Cancer Recurrence based on Circulating Tumor Cells and Epithelial–Mesenchymal Transition

2020 ◽  
Author(s):  
Jiani Yang ◽  
Jun Ma ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Shan Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Stratification ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Ca 125 ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract We aimed to determine prognosis value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in epithelial ovarian cancer(EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among training group(n=114) and validation group(n=38). By regression screening, both CTC counts(HR 1.187; 95%CI 1.098-1.752; p=0.012) and M-CTC(HR 1.098; 95%CI 1.047-1.320; p=0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive value for nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107) and the nomogram(p=0.0021) were drawn with significant difference. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016

scholarly journals Development and Validation for Prognostic Nomogram of Epithelial Ovarian Cancer Recurrence based on Circulating Tumor Cells and Epithelial–Mesenchymal Transition : A Prospective Study

2020 ◽  
Author(s):  
Jiani Yang ◽  
Jun Ma ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Shan Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Stratification ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
External Validation ◽  
Ca 125 ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis

Abstract BackgroundThe aim was to determine value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in risk stratification of epithelial ovarian cancer(EOC) recurrence.MethodsCTCs were prospectively analyzed among 118 patients with pathological diagnosed EOC from June 2017 to October 2019. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and then classify their subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram based on prognostic factors selected by Cox regression analysis, 88 patients were randomly assigned to a training group, and the rest 30 patients were included in external validation group. Risk stratification was performed through Kaplan–Meier survival analysis.ResultsBy multivariate regression screening, both CTC counts(HR, 1.187; 95%CI, 1.098-1.752; p=0.012) and M-CTC(HR, 1.098; 95%CI, 1.047-1.320; p=0.009) were demonstrated as independent prognosis factors for EOC recurrence. Apart from CTCs, other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of the internal and external validation for nomogram was 0.913 and 0.874. The AUC of ROC curves for nomogram with/without CTCs was 0.8705 and 0.8097, taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, the survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107), nomogram with(p=0.0021) and without(p=0.0002) CTCs were drawn with significant difference.ConclusionOverall, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTC counts, M-CTC and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.

scholarly journals Development and validation for prognostic nomogram of epithelial ovarian cancer recurrence based on circulating tumor cells and epithelial–mesenchymal transition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiani Yang ◽  
Jun Ma ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Shan Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Stratification ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Ca 125 ◽  
Predictive Values ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis

AbstractWe aimed to determine the prognosis value of circulating tumor cells (CTCs) undergoing epithelial–mesenchymal transition in epithelial ovarian cancer (EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal, and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among the training group (n = 114) and validation group (n = 38). By regression screening, both CTC counts (HR 1.187; 95% CI 1.098–1.752; p = 0.012) and M-CTC (HR 1.098; 95% CI 1.047–1.320; p = 0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites, and CA-125 were also selected (p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive values for the nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts (p = 0.0241), M-CTC (p = 0.0107), and the nomogram (p = 0.0021) were drawn with significant differences. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016.

scholarly journals Snail Driving Alternative Splicing of CD44 by ESRP1 Enhances Invasion and Migration in Epithelial Ovarian Cancer

2017 ◽  
Vol 43 (6) ◽  
pp. 2489-2504 ◽  
Author(s):  
Le Chen ◽  
Ying Yao ◽  
Lijuan Sun ◽  
Jiajia Zhou ◽  
Minmin Miao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Alternative Splicing ◽  
Epithelial Ovarian Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Protein ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Background/Aims: Our study aims to investigate the role, effect and mechanisms of ESRP1 (epithelial splicing regulatory protein 1) in epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). Methods: Microarray and immunohistochemical analysis of ESRP1 expression were performed in EOC cases. The correlations between ESRP1 expression and clinical factors on EOC were assessed. Lentivirus-mediated RNA interference and EGFP vector which contains ESRP1 gene were used to down-regulate and up-regulate ESRP1 expression in human EOC cell lines. Roles of ESRP1 in cell growth, migration and invasion of EOC cells were also measured by Cell Counting Kit-8 and Transwell systems in vitro and by a nude mice intraperitoneal transplantation model in vivo. Results: By the analysis of Gene Expression Omnibus (GEO) (p<0.05) and our own microarray data (p<0.001), ESRP1 expression in EOC was significantly different from normal ovarian tissue. It was abundant in the nuclei of cancer cells and in malignant lesions. However, it was weakly expressed or negative in both normal and benign lesions. High ESRP1 expression in EOC was associated with poor clinical outcomes. Decreased ESRP1 expression significantly increased cell migration and invasion both in vivo and in vitro. Snail strongly repressed ESRP1 transcription through binding to the ESRP1 promoter in EOC cells. Furthermore, ESRP1 regulated the expression of CD44s. Down-regulated ESRP1 resulted in an isoform switching from CD44v to CD44s, which modulated epithelial-mesenchymal transition (EMT) program in EOC. Up-regulatin of ESRP1 was detected in mesenchymal to epithelial transition (MET) in vivo. Conclusions: ESRP1 regulates CD44 alternative splicing during the EMT process which plays an important role in EOC carcinogenesis. In addition, ESRP1 is associated with disease prognosis in EOC.

scholarly journals Heterogeneity in Circulating Tumor Cells: The Relevance of the Stem-Cell Subset

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 483 ◽  
Author(s):  
Chiara Agnoletto ◽  
Fabio Corrà ◽  
Linda Minotti ◽  
Federica Baldassari ◽  
Francesca Crudele ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Subset ◽  
Intermediate Phenotype ◽  
Current Evidence ◽  
Early Event ◽  
Tumor Type ◽  
Mesenchymal Transition ◽  
Immunodeficient Mice

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial–mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity.

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