Peptidomic Analysis of Endometrial Tissue from Patients with Ovarian Endometriosis

Abstract

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.

Current biomarkers for the detection of endometriosis

“…For such a complex disease, a biomarker panel that combines several different markers will most likely be more accurate than any single biomarker in the diagnosis of endometriosis. [ 45 ] Studies have confirmed that some biomarker panels such as peptide peaks, [ 57 ] proteins, [ 58 ] and metabolites [ 39 ] have a promising prospect. And, with the development of new omics technology and multiple immunoassay techniques, more valuable biomarker panels may be discovered in the near future.…”

Peptidome Analysis of Umbilical Cord Mesenchymal Stem Cell (hUC-MSC) Conditioned Medium from Preterm and Term Infants

“…Although the false discovery rate (FDR) can detect differentially expressed peptides more accurately than p value, we would get very few peptides by FDR. Because we found that some studies also applied the P value to the analysis of peptides [94][95][96], we also used the p value in the study. Secondly, we preliminarily explored the functions of differentially expressed peptides on H 2 O 2 -treated A549 cells, and the cellular mechanisms and target molecules of these peptides are unknown, which need more detailed studies in vivo and in vitro.…”

Peptidome analysis of umbilical cord mesenchymal stem cell (hUC-MSC) conditioned medium from preterm and term infants

“…Although the false discovery rate (FDR) can detect differentially expressed peptides more accurately than p value, we would get very few peptides by FDR. Additionally, in order to identify more differentially expressed peptides, some studies also applied the p value to the analysis of peptides [ 53 , 54 ]. Thus, in some condition, it is also appropriate to use the p value.…”