Poster Presentation ESA-SRB-APEG-NZSE 2022

Plasma mass spectrometry-based proteomic biomarker discovery for endometriosis (#420)

Sushma Rao 1 , Berin Boughton 2 , Marten Snel 1 , Tara Pukala 3 , Meaghan Griffiths 4 , Peter Rogers 4 , Jane Girling 5 , Sarah Holdsworth-Carson 6
  1. South Australian Health and Medical Research Institute, University of Adeliade, Adelaide, SA, Australia
  2. Australian National Phenome Centre, Harry Perkins Institute of Medical Research, Murdoch, WA, Australia
  3. School of Physical Sciences, University of Adelaide, SA, Australia
  4. Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, VIC, Australia
  5. Department of Anatomy, University of Otago, Dunedin, New Zealand
  6. Julia Argyrou Endometriosis Centre, Epworth HealthCare, Ease Melbourne, VIC, Australia

Aims

Endometriosis diagnosis requires surgical visualisation of lesions and histopathology.  To date, no non-invasive diagnostic test has been validated.  Discovery research using sensitive high-throughput mass spectrometry (MS) has the potential to improve identification of clinically-relevant plasma proteins.  The aim of this study was to undertake MS-based proteomic biomarker discovery using  minimally-invasive plasma specimens from patients with and without endometriosis.

Methods

Blood was collected from patients attending the pelvic pain clinic (Royal Women’s Hospital) for laparoscopy (investigation/treatment of suspected endometriosis) (HREC Projects #10-43/16-43).  Information was collected from patients surveys (demographics/symptoms), medical records and surgeon/pathology reports.  Endometriosis status was confirmed using histopathology.  Plasma (EDTA-treated, stored at -80°C) from 60 endometriosis cases and 20 non-endometriosis controls were included in the study.  Following trypsin digestion, plasma peptides were analysed using a timsTOf Pro (Bruker Daltonics) mass spectrometer.  MaxQuant and Perseus were used for data processing and analysis.

Results

A total of 470 proteins were quantified and identified from plasma samples.  Compared to non-endometriosis controls, 26 proteins were significantly altered with endometriosis (FDR <0.05).  Nine proteins demonstrated a reduced abundance, while 17 proteins demonstrated a higher fold-change in the endometriosis group compared to controls.  We also identified 12 proteins that were absent in controls, but present in endometriosis cases.  Comparison between each stage of disease (rASRM Stage 1 to 4) versus controls, demonstrated a change in 11 proteins collectively (FDR <0.05).  The proteins of interest belonged to biological processes associated with immunity (complement system), angiogenesis, proliferation and cholesterol metabolism.

Conclusions

High-throughput MS-based proteomic biomarker discovery successfully identified 470 proteins in an endometriosis cohort.  Case-control analysis revealed significantly different protein expression profiles in association with endometriosis.  Further validation in an independent sample set is warranted.  Biomarker discovery using plasma proteomics offers a minimally-invasive approach to endometriosis diagnosis.