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Blood steroids are associated with prognosis and fat distribution in endometrial cancer
Ingvild L. Tangen a,b, Kristine E. Fasmer c,d, Gonda F. Konings e, Arthur Jochems e,f, Bert Delvoux e, Sofia Xanthoulea e, Tomasz Stokowy g, Elin Strand a,b, Hege F. Berg a,b, Seppo Auriola h, Jone Trovik a,b, Merja R. Häkkinen h, Ingfrid S. Haldorsen c,d, ENITEC i , Camilla Krakstad a,b, ,1, Andrea Romano e,1
a Department of Gynaecology and Obstetrics, Haukeland University Hospital, Bergen, Norway
b Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway
c Mohn Medical Imaging and Visualization Centre, Department of Radiology, Haukeland University Hospital, Bergen, Norway
d Section for Radiology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
e Department of Gynaecology and Obstetrics, GROW – School for Oncology & Developmental Biology, Maastricht University, Maastricht, the Netherlands
f The D-Lab: Decision Support for Precision Medicine, GROW – School for Oncology and Developmental Biology, Maastricht University Medical Centre, Universiteitssingel 40, 6229, ER, Maastricht, The Netherlands g Department of Clinical Science, University of Bergen, Bergen, Norway
h School of Pharmacy, University of Eastern Finland, Kuopio, Finland
i ENITEC: European Network for Individualised Treatment of Endometrial Cancer (within the European Society of Gynaecological Oncology
• Plasma levels for DHEA, DHEAS, P4, 21OH-P4 and E1S significantly increased in patients with long compared to short survival.
• Increased E2 plasma levels are associated with a high visceral fat percentage.
• Increased expression of genes involved in estrogen related signaling in tumors from patients with high E2 plasma levels
Background. Despite being a hormone dependent cancer, there is limited knowledge regarding the relation between level of steroids in blood and prognosis for endometrial cancer (EC) patients.
Methods. In this study we investigated plasma levels of 19 steroids using liquid-chromatography tandem mass-spectrometry in 38 postmenopausal EC patients, 19 with long, and 19 with short survival. We explored if estradiol levels were associated with specific abdominal fat distribution patterns and if transcriptional alterations related to estradiol levels could be observed in tumor samples.
Results. The plasma steroid levels for DHEA, DHEAS, progesterone, 21 OH progesterone and E1S were signif-icantly increased (all p b 0.05) in patients with long survival compared to short. Estradiol levels were significantly positively correlated with visceral fat percentage (p = 0.035), and an increased expression of genes involved in estrogen related signaling was observed in tumors from patients with high estradiol levels in plasma.
Conclusion. Several of the identified plasma steroids represent promising biomarkers in EC patients. The asso-ciation between increased estradiol levels and a high percentage of visceral fat indicates that visceral fat is a larger contributor to estradiol production compared to subcutaneous fat in this population.
Corresponding author at: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Norway, Department of Gynaecology and Obstetrics, Haukeland University Hospital, Jonas Lies vei 72, 5020 Bergen, Norway.
URL's: [email protected] (C. Krakstad).
1 Shared authorship.
The endometrium is sensitive to hormonal stimulation, and endo-metrial cancer (EC) is influenced by steroid hormones . Many of the established risk factors for developing EC are linked to hormonal stimu-lation including exogenous steroids, menstrual and reproductive factors and obesity [2,3]. Consistent with epidemiological data supporting that reproductive and hormonal factors are involved in the etiology of EC,