Abstract
BackgroundThe molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer.MethodsA case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter® PanCancer Pathways Panel, which contains 770 genes.ResultsThe expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9. The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%.ConclusionWe identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer.
Highlights
Endometrial cancer is the most prevalent gynecological tumor in developed countries, such as the USA and members of the European Union [1]
We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer
The aim of this study was to determine a genetic signature of recurrence risk in patients diagnosed with low- and intermediate-risk endometrial cancer in routine formalin-fixed paraffin-embedded (FFPE) tissue using a large panel of 770 genes covering 13 key cancer-related pathways by NanoString, a highly sensitive and robust methodology for RNA expression of FFPE samples
Summary
Endometrial cancer is the most prevalent gynecological tumor in developed countries, such as the USA and members of the European Union [1]. Countless risk stratifications associate staging with other variables, such as tumor grade, lymphovascular space invasion (LVSI) and histology, to define sequential adjuvant treatments [4]. It has been considered two distinct diseases since Bokhman’s publication in the early 1980s (low-grade endometrioid adenocarcinomas (type I, “well-differentiated”) and nonendometrioid carcinomas (type II, “poorly differentiated”) [5]. The Cancer Genome Atlas (TCGA) project changed the understanding of the carcinogenesis of this tumor, leading to four molecular subgroups with different prognoses (DNA polymerase epsilon (POLE) ultramutated, microsatellite instability (MSI) hypermutated, copy number (CN) low, and CN high) [6]. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer
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