Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis

A Vodolazkaia, Alexandra Vodolazkaia, Y El-Aalamat, D Popovic, Dušan Popović, A Mihalyi, Attila Mihalyi, Xavier Bossuyt, X Bossuyt, Cleophas Kyama, C M Kyama, A Fassbender, Amelie Fassbender, A Bokor, Attila Bokor, D Schols, Dominique Schols, Dana Huskens, D Huskens, C Meuleman, Christel Meuleman, K Peeraer, Karen Peeraer, C Tomassetti, Carla Tomassetti, Olivier Gevaert, O Gevaert, E Waelkens, Etienne Waelkens, A Kasran, Ahmad Kasran, Bart De Moor, B De Moor, T M D'Hooghe, Thomas D'Hooghe, Thomas D’Hooghe
Human Reproduction · 2012 · vol. 27(9) , pp. 2698–2711 · doi:10.1093/humrep/des234 · PMID:22736326 · W2130807780
article OA: bronze CC0 ⤵ 151 in-corpus citations
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Multivariate analysis of four plasma biomarkers, annexin V, VEGF, CA-125, and sICAM-1 or glycodelin, measured during menstruation, diagnosed ultrasound-undetectable endometriosis with 81-90% sensitivity and 63-81% specificity.

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Abstract

BACKGROUND: At present, the only way to conclusively diagnose endometriosis is laparoscopic inspection, preferably with histological confirmation. This contributes to the delay in the diagnosis of endometriosis which is 6-11 years. So far non-invasive diagnostic approaches such as ultrasound (US), MRI or blood tests do not have sufficient diagnostic power. Our aim was to develop and validate a non-invasive diagnostic test with a high sensitivity (80% or more) for symptomatic endometriosis patients, without US evidence of endometriosis, since this is the group most in need of a non-invasive test. METHODS: A total of 28 inflammatory and non-inflammatory plasma biomarkers were measured in 353 EDTA plasma samples collected at surgery from 121 controls without endometriosis at laparoscopy and from 232 women with endometriosis (minimal-mild n = 148; moderate-severe n = 84), including 175 women without preoperative US evidence of endometriosis. Surgery was done during menstrual (n = 83), follicular (n = 135) and luteal (n = 135) phases of the menstrual cycle. For analysis, the data were randomly divided into an independent training (n = 235) and a test (n = 118) data set. Statistical analysis was done using univariate and multivariate (logistic regression and least squares support vector machines (LS-SVM) approaches in training- and test data set separately to validate our findings. RESULTS: In the training set, two models of four biomarkers (Model 1: annexin V, VEGF, CA-125 and glycodelin; Model 2: annexin V, VEGF, CA-125 and sICAM-1) analysed in plasma, obtained during the menstrual phase, could predict US-negative endometriosis with a high sensitivity (81-90%) and an acceptable specificity (68-81%). The same two models predicted US-negative endometriosis in the independent validation test set with a high sensitivity (82%) and an acceptable specificity (63-75%). CONCLUSIONS: In plasma samples obtained during menstruation, multivariate analysis of four biomarkers (annexin V, VEGF, CA-125 and sICAM-1/or glycodelin) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81-90% and a specificity of 63-81% in independent training- and test data set. The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and/or pain without US evidence of endometriosis, scheduled for laparoscopy.

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Condition tags

mesh:D004715endometriosisinfertility

MeSH descriptors

Biomarkers Endometriosis Endometriosis Adult Biomarkers Case-Control Studies Edetic Acid Edetic Acid Endometriosis Female Humans Inflammation Laparoscopy Least-Squares Analysis Menstrual Cycle Middle Aged Models, Statistical Regression Analysis ROC Curve Sensitivity and Specificity

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