Dataset Information

ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer.

ABSTRACT: Endometrial cancer (EC) is the sixth deadliest cancer in women. The depth of myometrial invasion is one of the most important prognostic factors, being directly associated with tumor recurrence and mortality. In this study, ALCAM, a previously described marker of EC recurrence, was studied by immunohistochemistry at the superficial and the invasive tumor areas from 116 EC patients with different degree of myometrial invasion and related to a set of relevant epithelial and mesenchymal markers. ALCAM expression presented a heterogeneous functionality depending on its localization, it correlated with epithelial markers (E-cadherin/?-catenin) at the superficial area, and with mesenchymal markers at the invasive front (COX-2, SNAIL, ETV5, and MMP-9). At the invasive front, ALCAM-negativity was an independent marker of myometrial invasion. This negativity, together with an increase of soluble ALCAM in uterine aspirates from patients with an invasive EC, and its positive correlation with MMP-9 levels, suggested that ALCAM shedding by MMP-9 occurs at the invasive front. In vivo and in vitro models of invasive EC were generated by ETV5-overexpression. In those, we demonstrated that ALCAM shedding was related to a more invasive pattern and that full-ALCAM recovery reverted most of the ETV5-cells mesenchymal abilities, partially through a p-ERK dependent-manner.

SUBMITTER: Devis L

PROVIDER: S-EPMC5908276 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer.

Devis Laura L Martinez-Garcia Elena E Moiola Cristian P CP Quiles Maria Teresa MT Arbos Maria Antonia MA Stirbat Tomita Vasilica TV Brochard-Wyart Françoise F García Ángel Á Alonso-Alconada Lorena L Abal Miguel M Diaz-Feijoo Berta B Thomas William W Dufour Sylvie S Mancebo Gemma G Alameda Francesc F Reventos Jaume J Gil-Moreno Antonio A Colas Eva E

Oncotarget 20180330 24

Endometrial cancer (EC) is the sixth deadliest cancer in women. The depth of myometrial invasion is one of the most important prognostic factors, being directly associated with tumor recurrence and mortality. In this study, ALCAM, a previously described marker of EC recurrence, was studied by immunohistochemistry at the superficial and the invasive tumor areas from 116 EC patients with different degree of myometrial invasion and related to a set of relevant epithelial and mesenchymal markers. AL ...[more]

PMID: 29682175

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Project description:The purpose of the present study was to investigate the predictive value of metabolic syndrome in evaluating myometrial invasion (MI) in patients with endometrial cancer (EC). The study retrospectively included patients with EC who were diagnosed between January 2006 and December 2020 at the Department of Gynecology of Nanjing First Hospital (Nanjing, China). The metabolic risk score (MRS) was calculated using multiple metabolic indicators. Univariate and multivariate logistic regression analyses were performed to determine significant predictive factors for MI. A nomogram was then constructed based on the independent risk factors identified. A calibration curve, a receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the effectiveness of the nomogram. A total of 549 patients were randomly assigned to a training or validation cohort, with a 2:1 ratio. Data was then gathered on significant predictors of MI in the training cohort, including MRS [odds ratio (OR), 1.06; 95% confidence interval (CI), 1.01-1.11; P=0.023], histological type (OR, 1.98; 95% CI, 1.11-3.53; P=0.023), lymph node metastasis (OR, 3.15; 95% CI, 1.61-6.15; P<0.001) and tumor grade (grade 2: OR, 1.71; 95% CI, 1.23-2.39; P=0.002; Grade 3: OR, 2.10; 95% CI, 1.53-2.88; P<0.001). Multivariate analysis indicated that MRS was an independent risk factor for MI in both cohorts. A nomogram was generated to predict a patient's probability of MI based on the four independent risk factors. ROC curve analysis showed that, compared with the clinical model (model 1), the combined model with MRS (model 2) significantly improved the diagnostic accuracy of MI in patients with EC (area under the curve in model 1 vs. model 2: 0.737 vs. 0.828 in the training cohort and 0.713 vs. 0.759 in the validation cohort). Calibration plots showed that the training and validation cohorts were well calibrated. DCA showed that a net benefit is obtained from the application of the nomogram. Overall, the present study developed and validated a MRS-based nomogram predicting MI in patients with EC preoperatively. The establishment of this model may promote the use of precision medicine and targeted therapy in EC and has the potential to improve the prognosis of patients affected by EC.

Dataset Information

ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer.

Publications

ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer.

Similar Datasets

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