Blood steroids are associated with prognosis and fat distribution in endometrial cancer

Ingvild L. Tangen; Kristine E. Fasmer; Gonda F. Konings; Arthur Jochems; Bert Delvoux; Sofia Xanthoulea; Tomasz Stokowy; Elin Strand; Hege F. Berg; Seppo Auriola; Jone Trovik; Merja R. Hakkinen; Ingfrid S. Haldorsen; Camilla Krakstad; Andrea Romano; ENITEC

doi:10.1016/j.ygyno.2018.10.024

Blood steroids are associated with prognosis and fat distribution in endometrial cancer

Ingvild L. Tangen, Kristine E. Fasmer, Gonda F. Konings, Arthur Jochems, Bert Delvoux, Sofia Xanthoulea, Tomasz Stokowy, Elin Strand, Hege F. Berg, Seppo Auriola, Jone Trovik, Merja R. Hakkinen, Ingfrid S. Haldorsen, Camilla Krakstad^*, Andrea Romano, ENITEC

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 EIS were significantly increased (all p <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 association 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. (C) 2018 Elsevier Inc. All rights reserved.

Original language	English
Pages (from-to)	46-52
Number of pages	7
Journal	Gynecologic Oncology
Volume	152
Issue number	1
DOIs	https://doi.org/10.1016/j.ygyno.2018.10.024
Publication status	Published - Jan 2019

Keywords

Steroid profile
Endometrial cancer
Survival
Fat distribution
Gene expression
17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-1
SEX-HORMONES
LC-MS/MS
RISK
OBESITY
OVERWEIGHT
EXPRESSION
INCREASES
TISSUE
WOMEN

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10.1016/j.ygyno.2018.10.024

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Tangen, I. L., Fasmer, K. E., Konings, G. F., Jochems, A., Delvoux, B., Xanthoulea, S., Stokowy, T., Strand, E., Berg, H. F., Auriola, S., Trovik, J., Hakkinen, M. R., Haldorsen, I. S., Krakstad, C., Romano, A., & ENITEC (2019). Blood steroids are associated with prognosis and fat distribution in endometrial cancer. Gynecologic Oncology, 152(1), 46-52. https://doi.org/10.1016/j.ygyno.2018.10.024

@article{972f78fc42bd41218d1962d8e0c26a1e,

title = "Blood steroids are associated with prognosis and fat distribution in endometrial cancer",

abstract = "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 EIS were significantly increased (all p <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 association 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. (C) 2018 Elsevier Inc. All rights reserved.",

keywords = "Steroid profile, Endometrial cancer, Survival, Fat distribution, Gene expression, 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-1, SEX-HORMONES, LC-MS/MS, RISK, OBESITY, OVERWEIGHT, EXPRESSION, INCREASES, TISSUE, WOMEN",

author = "Tangen, {Ingvild L.} and Fasmer, {Kristine E.} and Konings, {Gonda F.} and Arthur Jochems and Bert Delvoux and Sofia Xanthoulea and Tomasz Stokowy and Elin Strand and Berg, {Hege F.} and Seppo Auriola and Jone Trovik and Hakkinen, {Merja R.} and Haldorsen, {Ingfrid S.} and Camilla Krakstad and Andrea Romano and ENITEC",

note = "Funding Information: This study was supported by Helse Vest , the University of Bergen , the Norwegian Cancer Society , the Research Council of Norway , Bergen Research Foundation , by the Dutch Cancer Society ({\textquoteleft}KWF Kankerbestrijding{\textquoteright}: www.kwf.nl ), contract number UM-13-5782 granted to RA and by Biocenter Finland (grant to AS). Funding Information: The Genomics Core Facility (GCF) at the University of Bergen, which is a part of the NorSeq consortium, provided services on high throughput sequencing and bioinformatics analysis; GCF is supported in part by major grants from the Research Council of Norway (grant no. 245979/F50 ) and Bergen Research Foundation (BFS) (grant no. BFS2016-genom ). Funding Information: This study was supported by Helse Vest, the University of Bergen, the Norwegian Cancer Society, the Research Council of Norway, Bergen Research Foundation, by the Dutch Cancer Society ({\textquoteleft}KWF Kankerbestrijding{\textquoteright}: www.kwf.nl), contract number UM-13-5782 granted to RA and by Biocenter Finland (grant to AS). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2019",

month = jan,

doi = "10.1016/j.ygyno.2018.10.024",

language = "English",

volume = "152",

pages = "46--52",

journal = "Gynecologic Oncology",

issn = "0090-8258",

publisher = "Elsevier Science",

number = "1",

}

Tangen, IL, Fasmer, KE, Konings, GF, Jochems, A, Delvoux, B, Xanthoulea, S, Stokowy, T, Strand, E, Berg, HF, Auriola, S, Trovik, J, Hakkinen, MR, Haldorsen, IS, Krakstad, C, Romano, A & ENITEC 2019, 'Blood steroids are associated with prognosis and fat distribution in endometrial cancer', Gynecologic Oncology, vol. 152, no. 1, pp. 46-52. https://doi.org/10.1016/j.ygyno.2018.10.024

TY - JOUR

T1 - Blood steroids are associated with prognosis and fat distribution in endometrial cancer

AU - Tangen, Ingvild L.

AU - Fasmer, Kristine E.

AU - Konings, Gonda F.

AU - Jochems, Arthur

AU - Delvoux, Bert

AU - Xanthoulea, Sofia

AU - Stokowy, Tomasz

AU - Strand, Elin

AU - Berg, Hege F.

AU - Auriola, Seppo

AU - Trovik, Jone

AU - Hakkinen, Merja R.

AU - Haldorsen, Ingfrid S.

AU - Krakstad, Camilla

AU - Romano, Andrea

AU - ENITEC

N1 - Funding Information: This study was supported by Helse Vest , the University of Bergen , the Norwegian Cancer Society , the Research Council of Norway , Bergen Research Foundation , by the Dutch Cancer Society (‘KWF Kankerbestrijding’: www.kwf.nl ), contract number UM-13-5782 granted to RA and by Biocenter Finland (grant to AS). Funding Information: The Genomics Core Facility (GCF) at the University of Bergen, which is a part of the NorSeq consortium, provided services on high throughput sequencing and bioinformatics analysis; GCF is supported in part by major grants from the Research Council of Norway (grant no. 245979/F50 ) and Bergen Research Foundation (BFS) (grant no. BFS2016-genom ). Funding Information: This study was supported by Helse Vest, the University of Bergen, the Norwegian Cancer Society, the Research Council of Norway, Bergen Research Foundation, by the Dutch Cancer Society (‘KWF Kankerbestrijding’: www.kwf.nl), contract number UM-13-5782 granted to RA and by Biocenter Finland (grant to AS). Publisher Copyright: © 2018 Elsevier Inc.

PY - 2019/1

Y1 - 2019/1

N2 - 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 EIS were significantly increased (all p <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 association 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. (C) 2018 Elsevier Inc. All rights reserved.

AB - 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 EIS were significantly increased (all p <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 association 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. (C) 2018 Elsevier Inc. All rights reserved.

KW - Steroid profile

KW - Endometrial cancer

KW - Survival

KW - Fat distribution

KW - Gene expression

KW - 17-BETA-HYDROXYSTEROID-DEHYDROGENASE TYPE-1

KW - SEX-HORMONES

KW - LC-MS/MS

KW - RISK

KW - OBESITY

KW - OVERWEIGHT

KW - EXPRESSION

KW - INCREASES

KW - TISSUE

KW - WOMEN

U2 - 10.1016/j.ygyno.2018.10.024

DO - 10.1016/j.ygyno.2018.10.024

M3 - Article

C2 - 30554934

SN - 0090-8258

VL - 152

SP - 46

EP - 52

JO - Gynecologic Oncology

JF - Gynecologic Oncology

IS - 1

ER -