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Genetic Characterization of Endometriosis Patients: Review of the Literature and a Prospective Cohort Study on a Mediterranean Population
Open AccessArticle

Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes

Translational ‘Omics and Biomarkers group, KK Research Centre, KK Women’s and Children’s Hospital, Singapore 229899, Singapore
Division of Obstetrics and Gynaecology, KK Women’s and Children’s Hospital, Singapore 229899, Singapore
OBGYN-Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
Department of Obstetrics and Gynaecology, Singapore General Hospital, Singapore 169608, Singapore
Department of Reproductive Medicine, KKH, Singapore 229899, Singapore
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: The Princess Grace Hospital, 42-52 Nottingham Place, London W1U 5NY, UK.
Current address: Singapore-MIT Alliance for Research and Technology, 1 CREATE Way, Singapore 138602, Singapore.
Int. J. Mol. Sci. 2020, 21(10), 3515;
Received: 20 April 2020 / Revised: 8 May 2020 / Accepted: 10 May 2020 / Published: 15 May 2020
(This article belongs to the Special Issue Endometriosis Research: From Bench to Bedside)
Endometriosis is a common inflammatory gynecological disorder which causes pelvic scarring, pain, and infertility, characterized by the implantation of endometrial-like lesions outside the uterus. The peritoneum, ovaries, and deep soft tissues are the commonly involved sites, and endometriotic lesions can be classified into three subphenotypes: superficial peritoneal endometriosis (PE), ovarian endometrioma (OE), and deep infiltrating endometriosis (DIE). In 132 women diagnosed laparoscopically with and without endometriosis (n = 73, 59 respectively), and stratified into PE, OE, and DIE, peritoneal fluids (PF) were characterized for 48 cytokines by using multiplex immunoassays. Partial-least-squares-regression analysis revealed distinct subphenotype cytokine signatures—a six-cytokine signature distinguishing PE from OE, a seven-cytokine signature distinguishing OE from DIE, and a six-cytokine-signature distinguishing PE from DIE—each associated with different patterns of biological processes, signaling events, and immunology. These signatures describe endometriosis better than disease stages (p < 0.0001). Pathway analysis revealed the association of ERK1 and 2, AKT, MAPK, and STAT4 linked to angiogenesis, cell proliferation, migration, and inflammation in the subphenotypes. These data shed new insights on the pathophysiology of endometriosis subphenotypes, with the potential to exploit the cytokine signatures to stratify endometriosis patients for targeted therapies and biomarker discovery. View Full-Text
Keywords: endometriosis; cytokines; peritoneal fluid; microenvironment; precision medicine endometriosis; cytokines; peritoneal fluid; microenvironment; precision medicine
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Zhou, J.; Chern, B.S.M.; Barton-Smith, P.; Phoon, J.W.L.; Tan, T.Y.; Viardot-Foucault, V.; Ku, C.W.; Tan, H.H.; Chan, J.K.Y.; Lee, Y.H. Peritoneal Fluid Cytokines Reveal New Insights of Endometriosis Subphenotypes. Int. J. Mol. Sci. 2020, 21, 3515.

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