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An Orthotopic Endometrial Cancer Model with Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells
Published on: September 12, 2019
Integration of Genomic and Clinical Retrospective Data to Predict Endometrioid Endometrial Cancer Recurrence
Jesus Gonzalez-Bosquet1, Sofia Gabrilovich1, Megan E McDonald1
1Department of Obstetrics and Gynecology, University of Iowa, 200 Hawkins Dr., Iowa City, IA 52242, USA.
Abstract:
Endometrial cancer (EC) incidence and mortality continues to rise. Molecular profiling of EC promises improvement of risk assessment and treatment selection. However, we still lack robust and accurate models to predict those at risk of failing treatment. The objective of this pilot study is to create models with clinical and genomic data that will discriminate patients with EC at risk of disease recurrence. We performed a pilot, retrospective, case−control study evaluating patients with EC, endometrioid type: 7 with recurrence of disease (cases), and 55 without (controls). RNA was extracted from frozen specimens and sequenced (RNAseq). Genomic features from RNAseq included transcriptome expression, genomic, and structural variation. Feature selection for variable reduction was performed with univariate ANOVA with cross-validation. Selected variables, informative for EC recurrence, were introduced in multivariate lasso regression models. Validation of models was performed in machine-learning platforms (ML) and independent datasets (TCGA). The best performing prediction models (out of >170) contained the same lncRNA features (AUC of 0.9, and 95% CI: 0.75, 1.0). Models were validated with excellent performance in ML platforms and good performance in an independent dataset. Prediction models of EC recurrence containing lncRNA features have better performance than models with clinical data alone.
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