Proteomics Analysis of Plasma for Early Diagnosis of Endometriosis

Amelie Fassbender, Fassbender A, Etienne Waelkens, Waelkens E, Nico Verbeeck, Cleophas M Kyama, Cleophas Kyama, Attila Bokor, Bokor A, Alexandra Vodolazkaia, Vodolazkaia A, Raf Van de Plas, Christel Meuleman, Meuleman C, Karen Peeraer, Carla Tomassetti, Olivier Gevaert, Fabian Ojeda, Ojeda F, De Moor B, Bart De Moor, Thomas D’Hooghe, D'Hooghe T, Thomas D'Hooghe
Obstetrics and gynecology · 2012 · vol. 119(2, Part 1) , pp. 276–285 · doi:10.1097/aog.0b013e31823fda8d · PMID:22270279 · W2158537745
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Proteomic analysis of plasma identified distinct peptide and protein profiles during the menstrual and luteal phases that can predict endometriosis, even when undetectable by ultrasound.

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This study evaluated whether proteomic analysis of plasma could predict endometriosis in infertile women with or without pelvic pain, particularly those with normal ultrasound results. Researchers analyzed 254 plasma samples from 89 control participants and 165 patients with histologically confirmed disease using mass spectrometry and machine learning models. The findings indicated that specific peptide and protein peaks during the menstrual or luteal phases achieved high sensitivity and specificity for diagnosing minimal-to-mild and moderate-to-severe disease stages. A noninvasive test based on menstrual phase plasma samples successfully identified ultrasonography-negative cases with strong diagnostic accuracy. This paper is centrally about endometriosis — specifically the development of a noninvasive plasma proteomics assay for early diagnosis in women with negative imaging.

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Abstract

OBJECTIVE: To test the hypothesis that differential surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein or peptide expression in plasma can be used in infertile women with or without pelvic pain to predict the presence of laparoscopically and histologically confirmed endometriosis, especially in the subpopulation with a normal preoperative gynecologic ultrasound examination. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis was performed on 254 plasma samples obtained from 89 women without endometriosis and 165 women with endometriosis (histologically confirmed) undergoing laparoscopies for infertility with or without pelvic pain. Data were analyzed using least squares support vector machines and were divided randomly (100 times) into a training data set (70%) and a test data set (30%). RESULTS: Minimal-to-mild endometriosis was best predicted (sensitivity 75%, 95% confidence interval [CI] 63-89; specificity 86%, 95% CI 71-94; positive predictive value 83.6%, negative predictive value 78.3%) using a model based on five peptide and protein peaks (range 4.898-14.698 m/z) in menstrual phase samples. Moderate-to-severe endometriosis was best predicted (sensitivity 98%, 95% CI 84-100; specificity 81%, 95% CI 67-92; positive predictive value 74.4%, negative predictive value 98.6%) using a model based on five other peptide and protein peaks (range 2.189-7.457 m/z) in luteal phase samples. The peak with the highest intensity (2.189 m/z) was identified as a fibrinogen β-chain peptide. Ultrasonography-negative endometriosis was best predicted (sensitivity 88%, 95% CI 73-100; specificity 84%, 95% CI 71-96) using a model based on five peptide peaks (range 2.058-42.065 m/z) in menstrual phase samples. CONCLUSION: A noninvasive test using proteomic analysis of plasma samples obtained during the menstrual phase enabled the diagnosis of endometriosis undetectable by ultrasonography with high sensitivity and specificity. LEVEL OF EVIDENCE: II.
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Objective

To test the hypothesis that differential surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein or peptide expression in plasma can be used in infertile women with or without pelvic pain to predict the presence of laparoscopically and histologically confirmed endometriosis, especially in the subpopulation with a normal preoperative gynecologic ultrasound examination.

Methods

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis was performed on 254 plasma samples obtained from 89 women without endometriosis and 165 women with endometriosis (histologically confirmed) undergoing laparoscopies for infertility with or without pelvic pain. Data were analyzed using least squares support vector machines and were divided randomly (100 times) into a training data set (70%) and a test data set (30%).

Results

Minimal-to-mild endometriosis was best predicted (sensitivity 75%, 95% confidence interval [CI] 63–89; specificity 86%, 95% CI 71–94; positive predictive value 83.6%, negative predictive value 78.3%) using a model based on five peptide and protein peaks (range 4.898–14.698 m/z) in menstrual phase samples. Moderate-to-severe endometriosis was best predicted (sensitivity 98%, 95% CI 84–100; specificity 81%, 95% CI 67–92; positive predictive value 74.4%, negative predictive value 98.6%) using a model based on five other peptide and protein peaks (range 2.189–7.457 m/z) in luteal phase samples. The peak with the highest intensity (2.189 m/z) was identified as a fibrinogen β-chain peptide. Ultrasonography-negative endometriosis was best predicted (sensitivity 88%, 95% CI 73–100; specificity 84%, 95% CI 71–96) using a model based on five peptide peaks (range 2.058–42.065 m/z) in menstrual phase samples.

Conclusion

A noninvasive test using proteomic analysis of plasma samples obtained during the menstrual phase enabled the diagnosis of endometriosis undetectable by ultrasonography with high sensitivity and specificity. LEVEL OF EVIDENCE: II

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Condition tags

endometriosisinfertility

MeSH descriptors

Blood Proteins Endometriosis Endometriosis Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Adult Blood Proteins Endometriosis Endometriosis Female Humans Menstruation Menstruation Predictive Value of Tests Proteomics Severity of Illness Index Ultrasonography Young Adult

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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