Combined mRNA microarray and proteomic analysis of eutopic endometrium of women with and without endometriosis
Abstract
BACKGROUND: An early semi-invasive diagnosis of endometriosis has the potential to allow early treatment and minimize disease progression but no such test is available at present. Our aim was to perform a combined mRNA microarray and proteomic analysis on the same eutopic endometrium sample obtained from patients with and without endometriosis. METHODS: mRNA and protein fractions were extracted from 49 endometrial biopsies obtained from women with laparoscopically proven presence (n= 31) or absence (n= 18) of endometriosis during the early luteal (n= 27) or menstrual phase (n= 22) and analyzed using microarray and proteomic surface enhanced laser desorption ionization-time of flight mass spectrometry, respectively. Proteomic data were analyzed using a least squares-support vector machines (LS-SVM) model built on 70% (training set) and 30% of the samples (test set). RESULTS: mRNA analysis of eutopic endometrium did not show any differentially expressed genes in women with endometriosis when compared with controls, regardless of endometriosis stage or cycle phase. mRNA was differentially expressed (P< 0.05) in women with (925 genes) and without endometriosis (1087 genes) during the menstrual phase when compared with the early luteal phase. Proteomic analysis based on five peptide peaks [2072 mass/charge (m/z); 2973 m/z; 3623 m/z; 3680 m/z and 21133 m/z] using an LS-SVM model applied on the luteal phase endometrium training set allowed the diagnosis of endometriosis (sensitivity, 91; 95% confidence interval (CI): 74-98; specificity, 80; 95% CI: 66-97 and positive predictive value, 87.9%; negative predictive value, 84.8%) in the test set. CONCLUSION: mRNA expression of eutopic endometrium was comparable in women with and without endometriosis but different in menstrual endometrium when compared with luteal endometrium in women with endometriosis. Proteomic analysis of luteal phase endometrium allowed the diagnosis of endometriosis with high sensitivity and specificity in training and test sets. A potential limitation of our study is the fact that our control group included women with a normal pelvis as well as women with concurrent pelvic disease (e.g. fibroids, benign ovarian cysts, hydrosalpinges), which may have contributed to the comparable mRNA expression profile in the eutopic endometrium of women with endometriosis and controls.
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Only one study randomly divided endometrial samples into training and test sets.
“Specifically, menstrual cycle phase of endometrial samples was not specified in several of the studies [132, 135], and only one randomly divided endometrial samples into training and test sets [131].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [131]
Several groups have reported unique proteomic profiles using the SELDI-TOF MS platform in eutopic endometrial specimens from women with and without endometriosis.
“Several groups have reported unique proteomic profiles using the SELDI-TOF MS platform in eutopic endometrial specimens from women with and without endometriosis [131, 132].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [131]
Fassbender et al. described a panel of differentially expressed peptide peaks (2072 m/z, 2973 m/z, 3623 m/z, 3680 m/z, and 21133 m/z) in the early secretory endometrial proteome of women with versus without endometriosis as diagnostic of endometriosis (all rAFS stages) with 91% sensitivity and 80% specificity.
“In a unique concomitant assessment of the endometrial transcriptome and proteome, Fassbender et al. described a panel of differentially expressed peptide peaks (2072 m/z, 2973 m/z, 3623 m/z, 3680 m/z, and 21133 m/z) in the early secretory endometrial proteome of women with versus without endometriosis as diagnostic of endometriosis (all rAFS stages) with 91% sensitivity and 80% specificity [131].”
From Update on biomarkers for the detection of endometriosis (2015) · cites this paper as [131]
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- Authors
- Fassbender, A., Verbeeck, N., Börnigen, D., Kyama, C. M., Bokor, A., Vodolazkaia, A., Peeraer, K., Tomassetti, C., Meuleman, C., Gevaert, O., Van de Plas, R., Ojeda, F., De Moor, B., Moreau, Y., Waelkens, E., & D'Hooghe, T. M.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- iMinds (BE)
- Jomo Kenyatta University of Agriculture and Technology (KE)
- Semmelweis University (HU)
- Stanford Medicine (US)
- KU Leuven (BE)
- ORCID
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05-03
- Volume
- 27
- Issue
- 7
- Pages
- 2020-2029
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2165696199
- Cited by
- 87
- References
- 40
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 10 · 2022: 5 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 8 · 2013: 7
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Keywords
- endometriosis, eutopic endometrium, endometriosis diagnosis, endometrial transcriptome, differential gene expression, least squares support vector machine, biomarkers, early diagnosis, menstrual cycle phases, sensitivity and specificity
- MeSH terms
- Adult, Biopsy, Endometriosis, Endometrium, Female, Humans, Peptides, Predictive Value of Tests, Retrospective Studies, RNA, Messenger, Biomarkers, Tumor, Biomarkers, Case-Control Studies, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Oligonucleotide Array Sequence Analysis, Proteomics, Support Vector Machine
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