Membrane expression of the death ligand trail receptors DR4 and DR5 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer

Endometrial cancer is the most common malignancy of the female genital tract and a major cause of morbidity and mortality in women. Early detection is key to ensuring good outcomes but a lack of minimally invasive screening tools is a significant barrier. Most endometrial cancers are obesity-driven and develop in the context of severe metabolomic dysfunction. Blood-derived metabolites may therefore provide clinically relevant biomarkers for endometrial cancer detection. In this study, we analysed plasma samples of women with body mass index (BMI) ≥ 30 kg/m2 and endometrioid endometrial cancer (cases, n = 67) or histologically normal endometrium (controls, n = 69), using a mass spectrometry-based metabolomics approach. Eighty percent of the samples were randomly selected to serve as a training set and the remaining 20% were used to qualify test performance. Robust predictive models (AUC > 0.9) for endometrial cancer detection based on artificial intelligence algorithms were developed and validated. Phospholipids were of significance as biomarkers of endometrial cancer, with sphingolipids (sphingomyelins) discriminatory in post-menopausal women. An algorithm combining the top ten performing metabolites showed 92.6% prediction accuracy (AUC of 0.95) for endometrial cancer detection. These results suggest that a simple blood test could enable the early detection of endometrial cancer and provide the basis for a minimally invasive screening tool for women with a BMI ≥ 30 kg/m2.

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Membrane expression of TRAIL receptors DR4, DR5, DcR1 and DcR2 in the normal endometrium, atypical endometrial hyperplasia and endometrioid adenocarcinoma: a tissue microarray study

Archives of Gynecology and Obstetrics ◽

10.1007/s00404-013-2840-x ◽

2013 ◽

Vol 288 (4) ◽

pp. 889-899 ◽

Cited By ~ 7

Author(s):

Leszek Gottwald ◽

Janusz Piekarski ◽

Robert Kubiak ◽

Jarosław Szwalski ◽

Grażyna Pasz-Walczak ◽

...

Keyword(s):

Tissue Microarray ◽

Endometrial Hyperplasia ◽

Endometrioid Adenocarcinoma ◽

Membrane Expression ◽

Normal Endometrium ◽

Atypical Endometrial Hyperplasia ◽

Microarray Study ◽

Trail Receptors

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Expression of HE4 in Endometrial Cancer and Its Clinical Significance

BioMed Research International ◽

10.1155/2015/437468 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Xiao Li ◽

Yiping Gao ◽

Mingzi Tan ◽

Huiyu Zhuang ◽

Jian Gao ◽

...

Keyword(s):

Endometrial Cancer ◽

Cancer Patients ◽

Clinical Stage ◽

Atypical Hyperplasia ◽

Clinicopathological Parameters ◽

Normal Endometrium ◽

Positive Expression ◽

Significant Difference ◽

Expression Rate ◽

Degree Of Differentiation

The main aims of this study were to determine the expression of human epididymis protein 4 (HE4) in endometrial cancer and to explore the relationships between HE4 expression, clinicopathological parameters, and prognosis. Immunohistochemistry was used to detect HE4 expression in 102 cases of endometrial cancer, 30 cases of endometrial atypical hyperplasia, and 20 cases of normal endometrium. The positive expression rate of HE4 in endometrial carcinoma was 84.62%, significantly higher than 66.67% in atypical hyperplasia (P<0.05) and 15.00% in normal endometrium (P<0.0.01). With the exception of stage II, HE4 expression in endometrial cancer showed an increasing tendency with increased clinical stage (P<0.05). The positive expression rate of HE4 increased with a decrease in the degree of differentiation. A statistically significant difference was observed between the highly differentiated group and the poorly differentiated group (P<0.05). Mortality in endometrial cancer patients with high HE4 expression was significantly higher than that in patients with low HE4 expression (P<0.05). Endometrial cancer patients with high HE4 expression have a poor prognosis.

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