Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis

Kuessel, Lorenz; Wenzl, René; Proestling, Katharina; Balendran, Sukirthini; Pateisky, Petra; st, Yotova; Yerlikaya, Gülen; Streubel, Berthold; Husslein, H

doi:10.1093/humrep/dex028

Cited by 47 publications

(52 citation statements)

References 38 publications

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“…The expression of BCL6 (Evans-Hoeker et al, 2016 ) has been reported to be altered in secretory phase endometrial biopsies and may be useful diagnostically, but this approach will require invasive biopsy procedures. Other possible diagnostic markers for endometriosis include CA-125 (Hirsch et al, 2017 ), VEGF, microRNAs, immunologic markers, and soluble ICAM levels (Acimovic et al, 2016 ; Vodolazkaia et al, 2016 ; Gagné et al, 2003 ; Matalliotakis et al, 2001 ; Kuessel et al, 2017 ; Mosbah et al, 2016 ; Bohler et al, 2007 ; Drosdzol-Cop et al, 2012 ; Wu et al, 2015 ); however, none of these can identify endometriosis patients with both high sensitivity and specificity. It is clear that the need for a non-invasive diagnostic marker or method remains, and it would appear that the analysis of ME may offer a path to develop such tests.…”

Section: Discussionmentioning

confidence: 99%

Analysis of menstrual effluent: diagnostic potential for endometriosis

Warren

Shih

Renteira

et al. 2018

Mol Med

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BackgroundEndometriosis is a chronic and underdiagnosed disease which affects 5–10% of women of childbearing age and is characterized by growth of endometrial tissue outside of the uterus, most often in the peritoneal cavity. Delay in diagnosis is a major problem for management of this disorder, and treatment is often not initiated until the disease has progressed for many years. Although the exact etiology of endometriosis remains unknown, retrograde menstruation is recognized as a common underlying factor leading to the deposit of menstrual effluent (ME) into the peritoneal cavity. Differences in the cellular biology and genetics of the cells within ME are therefore likely to explain why endometriosis develops in only a subset of women.MethodsPatients with and without endometriosis were consented to provide ME. ME was analyzed by flow cytometry for CD45- and CD45+ cell populations or used to isolate stromal fibroblast cells. ME-derived stromal fibroblast cells were assessed using decidualization assays following the addition of cAMP and IGFBP-1 concentrations in the culture supernatants were measured by ELISA. In addition, RNA was collected and analyzed by RNA-Seq and qPCR for markers of decidualization and to identify differentially expressed genes in ME-derived stromal fibroblast cells obtained from controls and subjects with endometriosis (±cAMP).ResultsFlow cytometry analysis of cell subsets within the CD45+ fraction of ME revealed a significant decrease in the number of uterine NK cells in endometriosis patients compared with controls (p < 0.01). No other significant differences within either the CD45+ or CD45- cell populations were observed. Most strikingly, ME-derived stromal fibroblast cells cultured from endometriosis subjects showed impaired decidualization potential compared with controls. Highly significant differences in decidualization response were detected by measuring IGFBP-1 production at multiple time points after cAMP stimulation (p = 0.0025 at 6 h; p = 0.0045 at 24 h; p = 0.0125 at 48 h). RNA-Seq and qPCR analyses were used to identify genes differentially expressed by ME-derived stromal fibroblast cells obtained from endometriosis and control subjects.ConclusionsMenstrual effluent can be useful for investigating the pathobiology of endometriosis and for developing a non-invasive diagnostic for endometriosis which may lead to earlier and more effective treatments for this common disorder.Electronic supplementary materialThe online version of this article (10.1186/s10020-018-0009-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Analysis of menstrual effluent: diagnostic potential for endometriosis

Warren

Shih

Renteira

et al. 2018

Mol Med

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“…ICAM1 is a cell surface glycoprotein, which binds to integrins [cycle of differentiation 11 (CD11)/CD18] to promote cell-cell adhesion. ICAM1 is regulated by STAT1 in type II serous papillary EC (36) and is elevated in endometriosis (37). Our previous study using the endometrial epithelial ECC-1 cells to model endometrial luminal epithelium during menstrual repair demonstrated galectin-7 at 2.5 µg/ml enhanced ECC-1 wound closure via integrin binding and upregulation of β-catenin, contactin and TGFβ1.…”

Section: Discussionmentioning

confidence: 94%

Galectin‑7 is elevated in endometrioid (type I) endometrial cancer and promotes cell migration

et al. 2018

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Endometrial cancer (EC) is the most commonly diagnosed gynecological malignancy in Australian women. Notably, its incidence and mortality rate is increasing. Despite this, there are limited treatment options for EC. Galectin-7 regulates tumorigenesis in numerous epithelial cancer types, but the role of galectin-7 has not been investigated in EC. It was hypothesized that galectin-7 expression would be altered in EC and contribute to the development of EC. Galectin-7 levels in EC and benign endometrium were quantified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA. The effect of recombinant galectin-7 (1 µg/ml) on cell adhesion, proliferation, apoptosis (xCELLigence and flow cytometry), migration (wound healing assay) and gene expression (RT-qPCR) was investigated using three human EC cell lines (Ishikawa, HEC1A and AN3CA). Galectin-7 gene and protein expression was significantly elevated in Grade 3 EC, compared with benign tissues. Galectin-7 was almost undetectable in Ishikawa and AN3CA cells, but highly expressed by HEC1A cells. Recombinant galectin-7 had no significant effect on cell proliferation or apoptosis in any cell line, but significantly reduced cell adhesion in Ishikawa (at 4 and 6 h) and AN3CA (at 2, 3, 4 and 6 h). Galectin-7 significantly promoted Ishikawa migration and significantly elevated collagen type IV α 1 chain and intercellular adhesion molecule 1 (ICAM1) gene expression during wound healing. The present study demonstrated that galectin-7 production increased in EC with increasing cancer grade; therefore, galectin-7 may promote the metastasis of EC by reducing cell-cell adhesion and enhancing cell migration.

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“…VCAM-1 and its counter receptors are expressed by both epithelial cells, such as eutopic and ectopic endometrial cells, and by cells of the immune system. Thus, VCAM-1 and its counter receptors may play roles in both the interaction between the endometrial cell and the peritoneal surface and the inflammation and immunological reaction that accompanies the disease process [46]. …”

Section: Discussionmentioning

confidence: 99%

Peptidomic Analysis of Endometrial Tissue from Patients with Ovarian Endometriosis

Xue

et al. 2018

Cell Physiol Biochem

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Background/Aims: Ovarian endometriosis (OvE) is ovarian cyst that is lined with endometrial tissue. They are found in 17–44% of women with endometriosis. Their clinical manifestations include pelvic pain, dysmenorrhea, dyspareunia, and infertility. Although the incidence of OvE has increased yearly, the exact pathogenesis of OvE is still unclear. We used peptidomics, an emerging branch of proteomics, to identify differentially expressed peptides in order to determine the possible roles of these peptides in the pathogenesis of OvE. Methods: The ectopic and eutopic endometria of OvE were used to extract peptides with 10-kDa molecular weight cutoff filters, and the peptide precursor proteins were then identified with PEAKS software, followed by quantification with the TMT labeling method and subsequent analysis by liquid chromatography-tandem mass spectrometry. Gene ontology (GO) analysis, pathway analysis, SMART, and SABLE were used to study the possible functions of these peptide according to their precursor proteins’ function. The effects of peptides derived from VCAM-1 (PDFV) on endometrial stromal cell (ESC) migration and invasion were examined with wound healing assays and Transwell assays and the expression of E-cadherin was detected by western blotting. Results: A total of 491 peptides were identified with abundant differences between the two groups of samples (p < 0.05, and absolute fold change ≥ 2). SMART and SABLE database showed that 42 of the 491 peptides were located in the conserved structural domains of their protein precursors and contained secondary structure and, among them, 2 peptides’ precursor proteins were associated with the cell proliferation. Additionally, 5 peptides’ precursor proteins were associated with endometriosis. Our study confirmed that PDFV promoted ESC migration and invasion and reduced E-cadherin expression (p < 0.05). Conclusion: PDFV and its precursor protein VCAM-1 may be involved in the process of OvE formation by reducing the expression of E-cadherin. The peptidomics analysis provides new insight for future studies of the mechanisms of OvE development.

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Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis

Abstract: The Ingrid Flick Foundation (Grant no. FA751C0801), which played no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests.

Cited by 47 publications

References 38 publications

Analysis of menstrual effluent: diagnostic potential for endometriosis

Analysis of menstrual effluent: diagnostic potential for endometriosis

Galectin‑7 is elevated in endometrioid (type I) endometrial cancer and promotes cell migration

Peptidomic Analysis of Endometrial Tissue from Patients with Ovarian Endometriosis

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