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Cited by 195Endometriosis Research and TreatmentEctopic Pregnancy Diagnosis and ManagementGynecological conditions and treatments

Update on biomarkers for the detection of endometriosis

Open access
Fassbender, Amelie, Burney, Richard O., F. O, Dorien, D’Hooghe, Thomas, Giudice, Linda·2015·BioMed Research International
DOI 10.1155/2015/130854PMC PMC4512573
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Abstract

Endometriosis is histologically characterized by the displacement of endometrial tissue to extrauterine locations including the pelvic peritoneum, ovaries, and bowel. An important cause of infertility and pelvic pain, the individual and global socioeconomic burden of endometriosis is significant. Laparoscopy remains the gold standard for the diagnosis of the condition. However, the invasive nature of surgery, coupled with the lack of a laboratory biomarker for the disease, results in a mean latency of 7–11 years from onset of symptoms to definitive diagnosis. Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression. The discovery of a sufficiently sensitive and specific biomarker for the nonsurgical detection of endometriosis promises earlier diagnosis and prevention of deleterious sequelae and represents a clear research priority. In this review, we describe and discuss the current status of biomarkers of endometriosis in plasma, urine, and endometrium.

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review concludes that no single biomarker or panel has been validated for noninvasive detection of endometriosis, and laparoscopy remains the diagnostic gold standard. It surveys blood, urine, and endometrial candidates, highlighting promising but largely unvalidated panels and the need for Phase II/III validation.

Key findings

  • Laparoscopy remains the gold standard, contributing to a mean latency of 7–11 years from symptom onset to definitive diagnosis; no blood biomarker or panel has been validated for clinical use.
  • CA-125 meta-analysis showed 50% sensitivity and 72% specificity for stage I–IV endometriosis, and 60% sensitivity with 80% specificity for stage III–IV disease; CA-125 is not specific because it is also elevated in ovarian cancer.
  • Several candidate panels report high accuracy but remain unvalidated, e.g. CA-125 + CA-19-9 + survivin mRNA had 87% sensitivity and a 10% false-positive rate; CA-125 + CCR1 mRNA + MCP-1 had 92.2% sensitivity and 81.6% specificity; a 4-marker panel (CA-125, VEGF, Annexin V, glycodelin/sICAM-1) showed 74–94% sensitivity and 55–75% specificity after initial validation.
  • Endometrial nerve fiber detection by PGP9.5 showed 98% sensitivity and 83% specificity in a double-blind pipelle study, but a clinical laboratory adoption detected nerve fibers in 9/45 (22%) histologically confirmed endometriosis cases and 6/21 (29%) women without endometriosis, raising specificity concerns.

Methods

  • Narrative review of the current status of endometriosis biomarkers in plasma, urine, and endometrium, framed by the four phases of biomarker development (Phase I preclinical discovery through Phase IV commercialization).
  • Synthesizes published studies and reported diagnostic performance metrics; no new primary data, systematic search strategy, or meta-analysis is described.
  • Main analysis is qualitative synthesis of candidate biomarkers, including glycoproteins, cytokines, oxidative stress markers, cell adhesion/invasion factors, angiogenesis markers, hormones, autoantibodies, miRNAs, proteomics, metabolomics, cell-free DNA, cell populations, urine markers, and endometrial markers.

Limitations

  • Stated in the paper: most endometriosis biomarker studies remain at Phase I, only a few reach Phase II, and Phase III/IV has not been reached; no noninvasive test is commercially available or validated.
  • Stated in the paper: common limitations include small sample size, suboptimal specimen characterization (e.g., no breakdown by menstrual phase or lesion phenotype), inconsistent sample handling/storage, and lack of reproducibility; proteomic technologies are costly, time-consuming, and need better standardization.
  • Evident from the text: as a narrative review, it does not use a systematic search or formal quality appraisal, and it relies on heterogeneous studies with differing assays, sample types, cycle phases, and populations, which limits comparability of reported sensitivities and specificities.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1155/2015/130854

Cites

148 of 148 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 198 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    CA-125 combined with IL-8 and TNF-α in the secretory phase had sensitivity of 89.7% and specificity of 71.1%.

    “CA-125 combined with interleukin-8 (IL-8) and tumor necrosis factors-α (TNF-α) in the secretory phase had a sensitivity of 89.7% and specificity of 71.1% in a study performed by Mihalyi and coworkers [36].”
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  • Premisecitation

    The sensitivity of CA-125 to detect all endometriosis stages is low.

    “In addition to this lack of specificity, the sensitivity to detect all endometriosis stages is low [31].”
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  • Premisenone given

    Phase IV commercialization has not yet been done successfully for noninvasive endometriosis biomarkers.

    “Product development by industry, which has not yet been done successfully for noninvasive endometriosis biomarkers.”
    Quote in the paperNot a substantial claim
  • Interpretationcitation

    Delay in diagnosis may have significant consequences in terms of disease progression.

    “Unfortunately, the delay in diagnosis may have significant consequences in terms of disease progression.”
    • Also stated in: § 1. Background · boosted
      “Delayed diagnosis and treatment has significant consequences, as endometriosis is more advanced in women whose diagnostic laparoscopy is delayed, supporting progression of disease over time [13].”
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  • Premisecitation

    Despite extensive research, no single biomarker nor a panel of biomarkers in peripheral blood has been validated as a diagnostic test for endometriosis.

    “Despite extensive research, no single biomarker nor a panel of biomarkers in peripheral blood has been validated as a diagnostic test for endometriosis [17, 20].”
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    Premisecitation

    A recent study showed significant increase of CA-125 (P=0.001), CA-19-9 (P=0.015), and CA-15-3 (P=0.017) in endometriosis cases (n=50) versus controls (n=35).

    “A recent study showed a significant increase of CA-125 (P = 0.001), CA-19-9 (P = 0.015), and CA-15-3 (P = 0.017) in endometriosis cases (n = 50) versus controls (n = 35) [42].”
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    Premisecitation

    CA-125 is not specific for endometriosis, being a tumor marker elevated in ovarian cancer.

    “However, CA-125 is not specific for endometriosis, being a tumor marker elevated in ovarian cancer [37, 38].”
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    Premisecitation

    Most endometriosis biomarker studies have remained at Phase I and only a few have made it to Phase II.

    “Overall, most endometriosis biomarker studies have remained at the level of Phase I [23] and only a few have made it to Phase II studies.”
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    Premisecitation

    There is consensus in the World Endometriosis Society that development of a reliable noninvasive test is one of the top research priorities in endometriosis.

    “Although there is consensus in the World Endometriosis Society that the development of a reliable noninvasive test is one of the top research priorities in endometriosis [11, 21]”
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    Premisecitation

    Endometriosis is more advanced in women whose diagnostic laparoscopy is delayed, supporting progression of disease over time.

    “endometriosis is more advanced in women whose diagnostic laparoscopy is delayed, supporting progression of disease over time [13].”
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    Premisecitation

    Since May et al., 2010, research in endometriosis biomarkers has accomplished successful validation of biomarkers in an independent sample dataset, but still no test for endometriosis is commercially available.

    “Since the extensive review of May et al., 2010, research in endometriosis biomarkers has accomplished the successful validation of biomarkers in an independent sample dataset [24], but still no test for endometriosis is commercially available.”
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    Premisecitation

    Blood is an interesting potential source of biomarkers because it allows repeated measurements, is easily obtained, and is highly suitable for high-throughput measurements.

    “Blood is an interesting potential source of biomarkers because it allows repeated measurements, is easily obtained, and is highly suitable for high-throughput measurements [29].”
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    Interpretationreasoning

    A non- or semi-invasive test would reduce the cost associated with endometriosis and improve quality of life of women with endometriosis by allowing early diagnosis.

    “In summary, a non- or semi-invasive test would not only reduce the cost associated with endometriosis but also improve the quality of life of women with endometriosis by allowing early diagnosis.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Ozhan et al. stated that a panel of CA-125, syntaxin-5, and laminin-1 had 90% sensitivity, 70% specificity, and 88.7% accuracy to distinguish endometriosis patients (n=60) from controls (n=20).

    “Ozhan et al. stated that a panel consisting of CA-125, syntaxin-5, and laminin-1 had 90% sensitivity, 70% specificity, and 88.7% accuracy to distinguish endometriosis patients (n = 60) from controls (n = 20) [41].”
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    Premisecitation

    Delay in diagnosis is due in part to presumptive treatment of pain with OCPs and NSAIDs, reluctance of physicians to refer women to gynecologists, reluctance of women to confront pain, and dismissal of pain as normal.

    “This delay in diagnosis is due, in part, to presumptive treatment of pain with oral contraceptives (OCPs) and nonsteroidal anti-inflammatory drugs (NSAIDs), as well as reluctance of physicians to refer women to gynecologists for definitive diagnosis, reluctance of women to confront their own pain for fear of a cancer diagnosis, and dismissal of pain, especially dysmenorrhea, as a “normal” event [”
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    Premisecitation

    CA-19-9 has been shown to be elevated in endometriosis and has comparable or lower sensitivity than CA-125 for detection of endometriosis.

    “Another ovarian tumor marker, CA-19-9, has been shown to be elevated in endometriosis and has a comparable or lower sensitivity than CA-125 for the detection of endometriosis [23].”
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    Premisecitation

    Combinations of CA-125 with urocortin, chlamydia antibody, CD23, and inflammatory cytokines did not provide sufficiently high sensitivity or specificity for endometriosis and results remained unvalidated.

    “CA-125 has been measured simultaneously with urocortin [34], chlamydia antibody [35], CD23 [39], and inflammatory cytokines [32]. However, none of these combinations provided a sufficiently high sensitivity or specificity for endometriosis and results remained unvalidated.”
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    Premisecitation

    Zn-alpha2-glycoprotein was identified by mass spectrometry as a possible biomarker for endometriosis and confirmed by ELISA to be differentially expressed (P=0.019) in an additional cohort of endometriosis patients (n=120) and healthy controls (n=20).

    “In a study conducted by Signorile and Baldi, Zinc (Zn)-alpha2-glycoprotein was identified by mass spectrometry (endometriosis cases n = 5, controls n = 5) as a possible biomarker for endometriosis and confirmed by ELISA to be differentially expressed (P = 0.019) in an additional cohort of endometriosis patients (n = 120) and healthy controls (n = 20) [45].”
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    Premisecitation

    A different study found a significant increase in serum glycodelin A in women with endometrioma (n=57) compared with control women (n=42) and demonstrated potential use as a biomarker for ovarian endometriosis with sensitivity of 82.1% and specificity of 78.4%.

    “A different study assessing glycodelin A found a significant increase in serum of women with endometrioma (n = 57) compared with control women undergoing sterilization or having benign ovarian cysts (n = 42) and demonstrated the potential use of glycodelin A as a biomarker for ovarian endometriosis with a sensitivity of 82.1% and a sensitivity of 78.4% [47].”
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    Premisecitation

    Follistatin has been shown to be increased in endometriosis patients, especially in a subgroup with ovarian endometrioma, and showed good sensitivity and specificity.

    “Follistatin, an inhibitor of activin, has been shown to be increased in endometriosis patients [23], especially in a subgroup of patients with ovarian endometrioma, and showed good sensitivity and specificity [43].”
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    Premisecitation

    YKL-40 was significantly elevated (P<0.001) in patients with endometriosis (n=53) compared with patients without endometriosis (n=35) and a positive correlation with disease severity was detected.

    “In a study by the same group, the inflammatory biomarker YKL-40 was significantly elevated (P < 0.001) in patients with endometriosis (n = 53) compared with patients without endometriosis (n = 35) and a positive correlation with disease severity was detected [53].”
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    Premisecitation

    In peripheral blood, IL-8, MCP-1, and RANTES showed potential as biomarkers, being significantly increased in endometriosis cases versus controls in 46.1%, 50%, and 75% of assessed studies, respectively.

    “In peripheral blood, IL-8, MCP-1, and RANTES showed potential as a biomarker, being significantly increased in endometriosis cases versus controls in, respectively, 46.1%, 50%, and 75% of the assessed studies [54].”
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    Premisecitation

    Reported sensitivity for Zn-alpha2-glycoprotein was 69.4% and specificity was 100%.

    “Reported sensitivity was 69.4% and specificity was 100% [45].”
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    Premisecitation

    In Vodolazkaia et al., univariate analysis showed differential expression of several cytokines and chemokines in 232 women with endometriosis and 121 controls, but no cytokines or chemokines were included in the final proposed panel after multivariate analysis.

    “In a study by Vodolazkaia et al., univariate analysis showed the differential expression of several cytokines and chemokines in 232 women with endometriosis and 121 controls [24]. However, no cytokines or chemokines were included in the final proposed panel of biomarkers after multivariate analysis [24].”
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    Premisecitation

    PEDF was significantly decreased in women with endometriosis (n=43) compared with women without endometriosis (n=28), independent of the phase of the cycle and correlated with pain symptoms.

    “In a study by Chen et al., PEDF was significantly decreased in women with endometriosis (n = 43) compared with women without endometriosis (n = 28), independent of the phase of the cycle and correlated with pain symptoms [71].”
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    Premisecitation

    Contrasting evidence exists on prolactin, leptin, LH, and adiponectin levels in endometriosis patients versus controls, showing either no difference, an increase (prolactin, leptin, LH) or a decrease (adiponectin).

    “Contrasting evidence exists on prolactin, leptin, luteinizing hormone (LH), and adiponectin levels in endometriosis patients versus controls, showing either no difference, an increase (prolactin, leptin LH) or a decrease (adiponectin) [23, 75, 76].”
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    Premisecitation

    Elevations of FGF-2, angiogenin, and soluble Flt-I (VEGFR-1) in serum of women with endometriosis have all been recorded.

    “Elevations of fibroblast growth factor-2 (FGF-2), angiogenin, and soluble Flt-I (VEGFR-1) in serum of women with endometriosis have all been recorded [23].”
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    Premisecitation

    Serum anti-PDIK1L and anti-syntaxin 5 autoantibodies were reported elevated in endometriosis patients.

    “Additionally, serum anti-PDIK1L [77] and anti-syntaxin 5 autoantibodies [78] were reported elevated in endometriosis patients.”
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    Premisecitation

    HGF was suggested to be elevated in women with endometriosis, although this was not confirmed in an additional study.

    “Hepatocyte growth factor (HGF) was suggested to be elevated in women with endometriosis [72], although this was not confirmed in an additional study [23, 73].”
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    • cites [72] 2003, Di Yi Jun Yi Da Xue Xue Bao

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    Premisecitation

    The potential use of circulating angiogenic cells as biomarkers for endometriosis has been examined, but no difference between endometriosis patients and controls could be detected.

    “Additionally, the potential use of circulating angiogenic cells as biomarkers for endometriosis has been examined, but no difference between endometriosis patients and controls could be detected [98].”
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    Premisecitation

    Proteomics technologies are costly and time-consuming, and there is a need for better standardization and reproducibility before they can be used reliably in clinical research projects.

    “These studies have shown promising results; however, proteomics technologies are costly and time-consuming [23], and there is a need for better standardization and reproducibility of proteomic technologies before they can be used reliably in clinical research projects [17].”
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    Premisecitation

    Reduced plasma levels of miR-17-5p, miR-20a, and miR-22 and elevated plasma levels of miR-16, miR-191, and miR-195 have been found in women with endometriosis compared with women without endometriosis.

    “Reduced plasma levels of miR-17-5p, miR-20a, and miR-22 [86] and elevated plasma levels of miR-16, miR-191, and miR-195 [87] have been found in women with endometriosis compared with women without endometriosis.”
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    Premisecitation

    Antiendometrial antibodies showed the most promising results, being more commonly present in endometriosis patients than in controls.

    “Both total immunoglobulin levels and antiendometrial antibodies have been investigated as potential biomarkers for endometriosis of which the latter showed the most promising results, being more commonly present in endometriosis patients than in controls [23].”
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    Interpretationcitation

    The finding that 70% of urine proteins originate directly from the urinary system legitimizes urine as a diagnostic medium but also suggests potential for reduced specificity, and it will be important to assess the ability of a urinary assay to differentiate endometriosis from other inflammatory conditions.

    “Though legitimizing urine as a diagnostic medium, this finding also suggests potential for reduced specificity, and it will be important to assess the ability of a urinary assay to differentiate endometriosis from other inflammatory conditions.”
    Quote in the paperSubstantial claim

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    Interpretationcitation

    This finding highlights both the prospect for miRNA dysregulation in the pathogenesis of endometrial disorders and the importance of accounting for menstrual cycle phase in the interpretation of miRNA profiles in biomarker discovery protocols.

    “This finding highlights both the prospect for miRNA dysregulation in the pathogenesis of endometrial disorders and the importance of accounting for menstrual cycle phase in the interpretation of miRNA profiles in biomarker discovery protocols.”
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    Premisecitation

    Relative to blood, urine has a significantly narrower dynamic range of proteins, allowing more rapid preparation of specimens for proteomic interrogation.

    “Relative to blood, urine evidences a significantly narrower dynamic range of proteins, thereby allowing more rapid preparation of specimens for proteomic interrogation.”
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    A systematic review of over 200 potential endometrial biomarkers revealed sensitivity and specificity ranging from 0 to 100%, with sensitivity and specificity reported in only 32 articles.

    “A systematic review of over 200 potential endometrial biomarkers, including hormones and their receptors (n = 29), cytokines (n = 25), factors identified through proteomics (n = 8), and histology (n = 10) revealed sensitivity and specificity (reported in only 32 articles) ranging from 0 to 100% [113].”
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    The endometrium evidences remarkable sex steroid-driven cyclic variation and regenerative capacity.

    “First, the endometrium evidences remarkable sex steroid-driven cyclic variation and regenerative capacity.”
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    Premisecitation

    The urine proteome is relatively stable for up to six hours at room temperature and for over 17 years stored at −70°C.

    “Additionally, the urine proteome is relatively stable for up to six hours at room temperature and for over 17 years stored at −70°C [105].”
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    Interpretationnone given

    MicroRNAs evidence differential expression in the endometrium of women with versus without endometriosis and therefore offer potential as an endometriosis biomarker.

    “MicroRNAs (miRNAs) evidence differential expression in the endometrium of women with versus without endometriosis and therefore offer potential as an endometriosis biomarker.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The dysregulation of miRNAs was cycle phase independent, though the relatively small sample size limited definitive correlation.

    “Interestingly, the dysregulation of miRNAs was cycle phase independent, though the relatively small sample size limited definitive correlation.”
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    Premisecitation

    Nerve fibers were first detected in peritoneal endometriotic lesions and these were thought to contribute to associated dysmenorrhea.

    “Nerve fibers were first detected in peritoneal endometriotic lesions and these were thought to contribute to associated dysmenorrhea [137].”
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    Premisecitation

    Functional endometrial layer nerve fibers assessed by PGP9.5 immunostaining were detected in 9 of 45 (22%) of histologically confirmed cases of endometriosis and in 6 of 21 (29%) of women without endometriosis.

    “Functional endometrial layer nerve fibers assessed by PGP9.5 immunostaining were detected in 9 of 45 (22%) of histologically confirmed cases of endometriosis and in 6 of 21 (29%) of women without endometriosis.”
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    Premisecitation

    This group further compared miRNA expression in women with mild and severe endometriosis and found increased endometrial expression of miR-21 and DICER in the more advanced stage of the disease.

    “This group further compared miRNA expression in women with mild and severe endometriosis and found increased endometrial expression of miR-21 and DICER in the more advanced stage of the disease [126].”
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    Interpretationreasoning

    These studies highlight molecular pathways that may be associated with the development of endometriosis as well as the changes in expression signature that exist in ectopically located endometrial tissue.

    “These studies highlight molecular pathways that may be associated with the development of endometriosis as well as the changes in expression signature that exist in ectopically located endometrial tissue.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Other miRNAs and predicted cognate mRNAs demonstrating differential expression in eutopic endometrium from women with and without endometriosis include miR-23a/CYP19A1 and miR-542-3p/COX2, miR-126/CRK and miR23a/NR5A1.

    “Other miRNAs and predicted cognate mRNAs demonstrating differential expression in eutopic endometrium from women with and without endometriosis include miR-23a/CYP19A1 and miR-542-3p/COX2 [128], miR-126/CRK [129] and miR23a/NR5A1 [130].”
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    Premisecitation

    The specificity of endometrial nerve fiber density was further challenged by the finding of similar endometrial innervation and neuronal growth fibers in women with adenomyosis, with expression reported to be more correlated with pelvic pain than diagnosis.

    “The specificity of endometrial nerve fiber density was further challenged by the finding of similar endometrial innervation and neuronal growth fibers in women with adenomyosis, with expression reported to be more correlated with pelvic pain than diagnosis [144].”
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    Interpretationcitation

    The adoption of validated, internationally agreed upon standard operating procedures (SOPs) for tissue sample collection, processing and storage, and standardized phenotypic and other patient data collection, are crucial to optimise sample quality, reduce variability, and enable cross-centre studies.

    “The adoption of validated, internationally agreed upon standard operating procedures (SOPs) for tissue sample collection, processing and storage, and standardized phenotypic and other patient data collection, are crucial to optimise sample quality, reduce variability, and enable cross-centre studies [17, 113, 148].”
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    Premisecitation

    A more recent study revealed 156 miRNAs differentially expressed between endometriotic tissue and normal endometrium, including twelve miRNAs known to be involved in fibrinolysis and angiogenesis.

    “A more recent study revealed 156 miRNAs differentially expressed between endometriotic tissue and normal endometrium, including twelve miRNAs known to be involved in fibrinolysis and angiogenesis [124].”
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    Premisecitation

    Many centres worldwide have been collecting blood or other body fluids such as peritoneal fluid, endometrial fluid, and menstrual fluid, as well as tissue samples-in particular ectopic and eutopic endometrium-from women with and without endometriosis, for a variety of research purposes.

    “Many centres worldwide have been collecting blood or other body fluids such as peritoneal fluid, endometrial fluid, and menstrual fluid, as well as tissue samples—in particular ectopic and eutopic endometrium—from women with and without endometriosis, for a variety of research purposes [145–147].”
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    • cites [146] source

      Not checked in the free run.

    • cites [147] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a study of sharp curettage and full thickness hysterectomy specimens, PGP9.5 immunostained nerve fibers were detected in the functional endometrial layer from all women with surgically confirmed endometriosis but none of the specimens from unaffected controls, and this finding was cycle phase independent.

    “In a study of sharp curettage and full thickness hysterectomy specimens, PGP9.5 immunostained nerve fibers were detected in the functional endometrial layer from all women with surgically confirmed endometriosis but none of the specimens from unaffected controls, and this finding was cycle phase independent [139].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [139] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    To date, the utility of miRNAs as biomarkers for endometriosis has not been specifically tested.

    “To date, the utility of miRNAs as biomarkers for endometriosis has not been specifically tested.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Reports of miR-23a expression in eutopic endometrium from women with and without endometriosis showed opposite directions of dysregulation, with one study involving proliferative endometrial specimens and the other including only early to midsecretory samples.

    “Notably, the reports of miR-23a expression in eutopic endometrium from women with and without endometriosis showed opposite directions of dysregulation, with one study involving proliferative endometrial specimens and the other including only early to midsecretory samples.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [128] source

      Not checked in the free run.

    • cites [130] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Recently, the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) has developed a consensus on standardisation and harmonisation of phenotypic surgical/clinical data and biologic sample collection methods in endometriosis research.

    “Recently, the World Endometriosis Research Foundation (WERF) Endometriosis Phenome and Biobanking Harmonisation Project (EPHect) has developed a consensus on standardisation and harmonisation of phenotypic surgical/clinical data and biologic sample collection methods in endometriosis research [146, 147, 149, 150].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [146] source

      Not checked in the free run.

    • cites [147] source

      Not checked in the free run.

    • cites [149] source

      Not checked in the free run.

    • cites [150] source

      Not checked in the free run.

49 of 49

  • The paper relies on this without support.

    MALDI-TOF does not allow direct identification of peptides or proteins that are differentially synthesized or secreted.

    “Importantly, MALDI-TOF does not allow direct identification of peptides or proteins that are differentially synthesized or secreted, which is fundamental to further validation and clinical assay development, although protein pattern recognition holds promise for the future.”

  • The paper relies on this without support.

    SELDI-TOF MS methodology provides differential proteomic profiles in the form of mass/charge (m/z) peaks without attendant characterization of the peptides or proteins.

    “Importantly, the SELDI-TOF MS methodology provides differential proteomic profiles in the form of mass/charge (m/z) peaks without attendant characterization of the peptides or proteins.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A panel of cytokines, rather than a single biomarker, improves sensitivity and specificity values, with some panels showing the ability to discriminate between different stages of disease.

    “The studies showed that a panel of cytokines, rather than a single biomarker, improve sensitivity and specificity values, with some panels showing the ability to discriminate between different stages of disease.”

    From Biomarkers in endometriosis: Challenges and opportunities (2017) · cites this paper as [71]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Reported panel accuracy does not match sensitivity, specificity, and group sizes

    Major

    With 60 patients and 20 controls, 90% sensitivity gives 54 correct patient classifications and 70% specificity gives 14 correct control classifications. Overall accuracy is therefore 68/80, or 85%, not 88.7%. The check repeats 90 three times to represent the 3:1 patient-to-control ratio.

    Reported 88.7 · recomputed 85

  • Nine of 45 cases is 20%, not 22%

    Minor

    The stated count gives 9/45 = 20%. The nearby figure of 6/21 = 29% is consistent with rounding.

    Reported 22 · recomputed 20

  • Two different sensitivities are given for glycodelin A

    Minor

    The sentence assigns two different sensitivity values to glycodelin A for the same stated diagnostic use, without distinguishing the measures.

3 of 3

Cites

2 retracted

Flagged first, then by citations

1 of the 149 references couldn’t be matched to a known paper.

Research works printed but not linked: 10

  1. 1927, American Journal of Obstetrics & Gynecology, 14, 442
  2. 2014, Biomarkers of endometriosis, 321
  3. 10.1093/humupd/dmq009 · DOI · Paper page
  4. 2008, Health economics of endometriosis, 1
  5. 2011, Minerva Ginecologica, 63, 195
  6. 2013, International Journal of Fertility and Sterility, 7, 96
  7. 2003, Di Yi Jun Yi Da Xue Xue Bao, 23, 757
  8. 2008, Anticancer Research, 28, 119
  9. 2014, Biomarkers of endometriosis
  10. 2000, Journal of Clinical Endocrinology and Metabolism, 85, 3292

Cited by

Sorted by citations

Related

Authors
Fassbender, A., Burney, R. O., F. O, D., D’Hooghe, T., & Giudice, L.
Affiliations
  • Universitair Ziekenhuis Leuven (BE)
  • Madigan Army Medical Center (US)
  • Department of Development and Regeneration, Organ Systems, KU Leuven, 3000 Leuven, Belgium
  • University of California, San Francisco (US)
Corresponding author
  • D’Hooghe, Thomas
  • Giudice, Linda
ORCID
Venue
BioMed Research International
Publisher
Hindawi Limited
Published
2015
Volume
2015
Pages
1-14
ISSN
  • 1110-7243 (ISSN-L)
  • 2314-6133
  • 2314-6141
DOI
10.1155/2015/130854
PMC
PMC4512573
OpenAlex
W1935876281
Semantic Scholar
49184ea27e4695119ebaa60bce32622318c29b7e
Cited by
195
References
149
Citations by year
2026: 6 · 2025: 7 · 2024: 10 · 2023: 11 · 2022: 26 · 2021: 25 · 2020: 27 · 2019: 23 · 2018: 18 · 2017: 18 · 2016: 22 · 2015: 2
FWCI
3.01
Type
journal article
Language
en
Open access
Licence
Locations
  • BioMed Research International (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD055764)
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 › Gynecological conditions and treatments
Keywords
endometriosis, biomarkers, early diagnosis, plasma biomarkers, urinary biomarkers, endometrium, infertility, pelvic pain, delayed diagnosis
MeSH terms
Endometriosis, Endometrium, Female, Humans, Sensitivity and Specificity, Reproducibility of Results, Biomarkers, Early Diagnosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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