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?

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.

Proximity Extension Assay in Combination with Next-Generation Sequencing for High-throughput Proteome-wide Analysis

“…The technology is based on the already proven high-multiplex PEA technology that has primarily been applied for screening of proteins in blood ( 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ) but is now also used for other sample matrices, e.g. , CSF ( 29 ), cell ( 30 ) and tissue ( 31 ) lysate, saliva ( 32 ), urine ( 33 ), interstitial fluid ( 34 ), cell culture media ( 35 ), peritoneal fluid ( 36 ), breast milk ( 37 ), BALF ( 38 ) and synovial fluid ( 39 ). Moreover, as minimal sample volumes are required, the technology has also been applied to samples of minimal sample volume, for example, single cells ( 40 ), exosomes ( 41 ), dried blood spots ( 42 ), aqueous humor ( 43 ) and fine-needle biopsies ( 44 ).…”

Endometrial stem/progenitor cells and their roles in immunity, clinical application, and endometriosis

“…Endometriosis alters the peritoneal microenvironment of women, in which the immune response, angiogenesis, cell proliferation, cell adhesion, and apoptosis are uniquely regulated in peritoneal fluid (PF). A specific protein expression pattern is present in PF with deep infiltrating endometriosis (DIE) compared in PF with non-DIE [ 124 ]. The detached endometrial fragments flow into the pelvic cavity, where they directly interact with cytokines in PF [ 125 ] to secrete chemokines [ 126 ] and to form a feedforward loop [ 127 ], which eventually induces the infiltration of immune cells and BMDSCs [ 128 ].…”

A Targeted Proteomics Approach for Screening Serum Biomarkers Observed in the Early Stage of Type I Endometrial Cancer

“…In endometriosis, PEA technology identified seven proteins up-regulated (IL-6, IL-8, CCL 19, SCF, VEGF-D, IL-6RA, MIA9) and ten proteins down-regulated (ICOSLG, EGFR, SELE, ErbB2/HER2, IL-6RA, VEGFR-2, Flt3L, CXCL10, HE4, FR-alpha). Moreover, in endometriosis patients, dysregulation of these proteins has been reported to induce immune response modulation, angiogenesis, cell proliferation, cell adhesion and inhibition of apoptosis [ 38 ].…”

“…The Olink PEA platform is a high-multiplex protein biomarker platform with a high-throughput capacity with high specificity and sensitivity in combination with minimal sample volume [ 32 ]. This powerful technology has been applied for the screening of proteins in blood [ 33 , 34 ], and on other matrices, e.g., cells [ 35 ], urine [ 36 ], peritoneal fluid [ 37 ], and exosomes [ 38 ]. Moreover, recently it has been applied to study immunological mechanisms in the multisystem inflammatory syndrome in children with COVID-19 [ 39 ].…”