Does the Use of the "Proseek® Multiplex Oncology I Panel" on Peritoneal Fluid Allow a Better Insight in the Pathophysiology of Endometriosis, and in Particular Deep-Infiltrating Endometriosis?

Alexandra Perricos,Gabriel Beikircher,Heinrich Husslein,Andreas Weinhaeusel,René Wenzl,Lorenz Kuessel,Manuela Gstoettner,Thomas Eiwegger

doi:10.3390/jcm9062009

Abstract

Endometriosis appears to share certain cancer-related processes, such as cell attachment, invasion, proliferation and neovascularization, some of which can also be found in other healthy tissues. In order to better understand the altered milieu of the peritoneal cavity, while acknowledging the reported similarities between endometriosis and neoplastic processes, we applied a multiplex oncology panel to search for specific biomarker signatures in the peritoneal fluid of women with endometriosis, women with deep-infiltrating endometriosis (DIE), as well as controls. In total, 84 patients were included in our study, 53 women with endometriosis and 31 controls. Ninety-two proteins were measured in prospectively collected peritoneal fluid (PF) samples, using the “Proseek® Multiplex Oncology I Panel”. We first compared patients with endometriosis versus controls, and in a second step, DIE versus endometriosis patients without DIE. Out of the 92 analyzed proteins, few showed significant differences between the groups. In patients with endometriosis, ICOS ligand, Endothelial growth factor, E-selectin, Receptor tyrosine-protein kinase erbB-2, Interleukin-6 receptor alpha, Vascular endothelial growth factor receptor 2, Fms-related tyrosine kinase 3 ligand, C-X-C motif chemokine 10, Epididymal secretory protein E4 and Folate receptor-alpha were decreased, while Interleukin-6 and Interleukin-8 were increased compared to controls. Looking at patients with DIE, we found Chemokine ligand 19, Stem cell factor, Vascular endothelial growth factor D, Interleukin-6 receptor alpha and Melanoma inhibitory activity to be increased compared to endometriosis patients without DIE. We have shown a distinct regulation of the immune response, angiogenesis, cell proliferation, cell adhesion and inhibition of apoptosis in PF of patients with endometriosis compared to controls. The specific protein pattern in the PF of DIE patients provides new evidence that DIE represents a unique entity of extrauterine endometriosis with enhanced angiogenetic and pro-proliferative features.

Highlights

Endometriosis affects 6–10% of women of reproductive age [1] and is characterized by the implantation and proliferation of endometrial tissue outside the uterine cavity [1,2]
Concerning the inhibition of apoptosis and cell proliferation activity of endometriotic cells, we found four factors to be decreased in peritoneal fluid (PF) of endometriosis patients compared to controls: The epidermal growth factor receptor (EGFR) is expressed on many different cell types
While angiogenesis is believed to play an important role in the formation of endometriotic lesions, we found the vascular endothelial growth factor receptor 2 (VEGFR-2) to be significantly underexpressed in the PF of affected women compared to controls, and we found no significant difference in its ligand VEGF between the two groups, which does not match the results of previous studies [44]

Summary

Introduction

Endometriosis affects 6–10% of women of reproductive age [1] and is characterized by the implantation and proliferation of endometrial tissue outside the uterine cavity [1,2]. A panel of potential oncological target proteins identified promising biomarkers for the diagnosis of colorectal and ovarian cancer [22,23] This panel simultaneously analyzed 92 proteins that play a role in a magnitude of cancer-related processes including angiogenesis, apoptotic processes, cell proliferation, immune response, invasion and chemotaxis. This method has already been applied in several studies investigating malignant diseases [24,25], very few studies have examined the relevance of multiplex technologies in the field of endometriosis [26,27]. In order to better understand the altered milieu of the peritoneal cavity, while acknowledging the reported similarities between endometriosis and neoplastic processes, we (1) applied the “Proseek® Multiplex Oncology I Panel” to search for specific biomarker signatures in peritoneal fluid (PF) of women with endometriosis compared to controls, and (2) differences between DIE and endometriosis without any sign of DIE

Patients

Sample Analysis

Results

Conclusions