Combined mRNA microarray and proteomic analysis of eutopic endometrium of women with and without endometriosis

TY - JOUR

T1 - Combined mRNA microarray and proteomic analysis of eutopic endometrium of women with and without endometriosis

AU - Fassbender, A

AU - Verbeeck, N

AU - Börnigen, D

AU - Kyama, C M

AU - Bokor, A

AU - Vodolazkaia, A

AU - Peeraer, K

AU - Tomassetti, C

AU - Meuleman, C

AU - Gevaert, O

AU - Van de Plas, R

AU - Ojeda, F

AU - De Moor, B

AU - Moreau, Y

AU - Waelkens, E

AU - D'Hooghe, T M

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

KW - Adult

KW - Biomarkers

KW - Biomarkers, Tumor

KW - Biopsy

KW - Case-Control Studies

KW - Endometriosis

KW - Endometrium

KW - Female

KW - Humans

KW - Oligonucleotide Array Sequence Analysis

KW - Peptides

KW - Predictive Value of Tests

KW - Proteomics

KW - RNA, Messenger

KW - Retrospective Studies

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Support Vector Machine

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/humrep/des127

DO - 10.1093/humrep/des127

M3 - SCORING: Journal article

C2 - 22556377

VL - 27

SP - 2020

EP - 2029

JO - HUM REPROD

JF - HUM REPROD

SN - 0268-1161

IS - 7

ER -