Update on Biomarkers for the Detection of Endometriosis

In the paper

“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].”

What the sources say

• Not checked yetcites [36] source

In the paper

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

What the sources say

• Not checked yetcites [31] source

In the paper

“Product development by industry, which has not yet been done successfully for noninvasive endometriosis biomarkers.”

In the paper

“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].”

What the sources say

• Not checked yetcites [13] source

In the paper

“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].”

What the sources say

• Not checked yetcites [17] source
• Not checked yetcites [20] source

In the paper

“A panel of CA-125, chemokine receptor (CCR) type-1 mRNA, and monocyte chemoattractant protein- (MCP) 1 showed a sensitivity of 92.2% and specificity of 81.6% to detect endometriosis [40].”

What the sources say

• Not checked yetcites [40] source

In the paper

“A clinically reliable test for endometriosis can be expected to have a profound impact on reduction of health care and individual costs by [18]reducing time to diagnosis and the time wasted to see numerous health care professionals;subsequently reducing the time before individualized specialist care is invoked;subsequently reducing expensive hit-and-miss treatments;subsequently reducing expensive”

What the sources say

• Not checked yetcites [18] 2014
• Not checked yetcites [25] 2008

In the paper

“longitudinal placebo-controlled trials with second look laparoscopy have demonstrated that 71–83% of untreated lesions will progress or remain stable over a 12-month period [14].”

What the sources say

• Not checked yetcites [14] 1994, Fertility and Sterility source

In the paper

“However, all these results remain to be validated.”

In the paper

“According to a meta-analysis by Mol et al., the sensitivity for stage I–IV endometriosis was 50% and specificity was 72%.”

What the sources say

• Not checked yetcites [31] source

In the paper

“Putative endometriosis biomarkers are mostly glycoproteins, growth or adhesion factors, hormones, or proteins related to immunology or angiogenesis [17, 23, 30].”

What the sources say

• Not checked yetcites [17] source
• Not checked yetcites [23] source
• Not checked yetcites [30] source

In the paper

“For stage III-IV endometriosis, a sensitivity of 60% could be obtained with a specificity of 80% [31].”

What the sources say

• Not checked yetcites [31] source

In the paper

“the development of such a test, from initial biomarker discovery to a clinically approved biomarker assay is a long, difficult, and uncertain process [22]”

What the sources say

• Not checked yetcites [22] source

In the paper

“Laparoscopy remains the gold standard for the diagnosis of the condition.”

• Also stated in: § 1. Background · plain

  “the gold standard for the diagnosis of endometriosis remains direct visualization of lesions at surgery preferably coupled with histologic confirmation of endometrial glands and stroma in biopsies of suspected lesions”

• Also stated in: § 2. Diagnostic Test for Endometriosis · plain

  “The gold standard for the diagnosis of peritoneal endometriosis has been visual inspection by laparoscopy followed by histological confirmation [7].”

What the sources say

• Not checked yetcites [7] source

In the paper

“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.”

• Also stated in: § 1. Background · boosted

  “The requirement for invasive surgery for the diagnosis of peritoneal implants strongly contributes to an average latency of 7–11 years from onset of symptoms to definitive diagnosis [3, 11].”

What the sources say

• Not checked yetcites [3] source
• Not checked yetcites [11] source

In the paper

“The combination of CA-125, CA-19-9, and survivin mRNA showed promise, boasting a sensitivity of 87% and a 10% false positive rate [33].”

What the sources say

• Not checked yetcites [33] source

In the paper

“This phase establishes the diagnostic accuracy and predictive value in the target population, but this phase has not yet been reached in endometriosis biomarker research.”

In the paper

“At present, such a test does not exist [17, 20].”

What the sources say

• Not checked yetcites [17] source
• Not checked yetcites [20] source

In the paper

“In a study by de Sanctis et al., mRNA levels of MMP-3 were significantly higher in stage II–IV endometriosis cases than in controls [66].”

What the sources say

• Not checked yetcites [66] source

In the paper

“Significantly increased IL-4 serum values have been found in adolescents with endometriosis [52].”

What the sources say

• Not checked yetcites [52] source

In the paper

“A study by Mihalyi et al. found a panel consisting of luteal plasma levels of IL-8, TNF-α, and CA-125 that was able to distinguish between 201 women with endometriosis and 93 controls with a normal pelvis with a sensitivity of 89.7% and a specificity of 71.1% [36].”

What the sources say

• Not checked yetcites [36] source

In the paper

“For CA-19-9 a significant positive correlation with disease severity was found [42].”

What the sources say

• Not checked yetcites [42] source

In the paper

“Recently, a panel of 4 biomarkers (CA-125, VEGF, Annexin V, and glycodelin/soluble intercellular adhesion molecule (sICAM)-1) showed a sensitivity of 74–94% and a specificity of 55–75% in a training set and after initial validation in an independent test set [24].”

What the sources say

• Not checked yetcites [24] source

In the paper

“Levels of the sICAM-I have been suggested to rise during early stages of endometriosis (I-II) and decrease at stage III-IV [23].”

What the sources say

• Not checked yetcites [23] source

In the paper

“The inflammatory marker C-reactive protein (CRP) has been shown to be upregulated [23], especially when examined with a high sensitivity assay making it possible to detect subclinical inflammation in women with endometriosis [50].”

What the sources say

• Not checked yetcites [23] source
• Not checked yetcites [50] source

In the paper

“However, a follow-up study could not reproduce these results [44].”

What the sources say

• Not checked yetcites [44] source

In the paper

“MMP-2 [63] and MMP-9 [64] have been found to be significantly increased in endometriosis patients versus controls.”

What the sources say

• Not checked yetcites [63] source
• Not checked yetcites [64] source

In the paper

“The same study showed similar levels of MMP-9 and vascular endothelial growth factor A (VEGF-A) mRNA among cases and controls [66].”

What the sources say

• Not checked yetcites [66] source

In the paper

“Glycodelin A, a promoter of neovascularization and cell proliferation, was examined in follicular phase serum of adolescent girls with endometriosis (n = 33) aged 13–19 alongside TNF-α and IL-6, but none of these proteins showed a different expression compared with adolescents without endometriosis (n = 17) [46].”

What the sources say

• Not checked yetcites [46] source

In the paper

“Values of T-helper pathway related interleukins IL-10, IL-12, IL-17, and IL-23 levels were comparable between infertile controls and endometriosis patients with infertility [49].”

What the sources say

• Not checked yetcites [49] source

In the paper

“ROC curve analysis showed that the area under the curve was the highest for CA-125 (0.938) [42].”

What the sources say

• Not checked yetcites [42] source

In the paper

“Follow-up of patients with advanced endometriosis showed reduced VEGF-A levels after laparoscopic excision of the lesions [68, 69].”

What the sources say

• Not checked yetcites [68] source
• Not checked yetcites [69] source

In the paper

“Women with endometriosis might experience increased oxidative stress in the pelvic cavity due to the retrograde flow of menstrual erythrocytes that release iron upon rupture [55].”

What the sources say

• Not checked yetcites [55] source

In the paper

“Correspondingly, sICAM-I has been included in a panel with three other markers to diagnose endometriosis cases that could not be identified by preoperative ultrasound [24].”

What the sources say

• Not checked yetcites [24] source

In the paper

“Its usefulness as biomarker for endometriosis is unclear, as some studies show elevated blood levels in endometriosis patients while other studies do not record a significant difference [23, 67].”

What the sources say

• Not checked yetcites [23] source
• Not checked yetcites [67] 2013, International Journal of Fertility and Sterility

In the paper

“In a study by Panoulis et al., no difference in the serum expression of the inflammatory markers CD40, CD40L and a disintegrin and metalloproteinase domain 8 (ADAM8) was detected between endometriosis patients (n = 47) and controls (n = 29) [48].”

What the sources say

• Not checked yetcites [48] 2011, Minerva Ginecologica

In the paper

“In addition, the cell adhesion molecule osteopontin was elevated in plasma for all disease stages [60, 61].”

What the sources say

• Not checked yetcites [60] source
• Not checked yetcites [61] source

In the paper

“Moreover, advanced endometriosis is correlated with a higher MMP-2 expression [65].”

What the sources say

• Not checked yetcites [65] source

In the paper

“However, no consensus exists on whether cytokines are suitable to discriminate endometriosis patients from patients with other pelvic pathology [24].”

What the sources say

• Not checked yetcites [24] source

In the paper

“At a cut-off value of 251.18 pg/mL, its sensitivity to predict endometriosis was 65% and the specificity was 58.3% [42].”

What the sources say

• Not checked yetcites [42] source

In the paper

“However, other studies could not find an upregulation [23, 51].”

What the sources say

• Not checked yetcites [23] source
• Not checked yetcites [51] source

In the paper

“In a study comprising patients with ovarian endometriosis (n = 40), eight metabolites and 81 metabolite ratios were significantly higher in the endometriosis group compared with healthy controls undergoing laparoscopy for sterilization (n = 52) [93].”

What the sources say

• Not checked yetcites [93] source

In the paper

“A study comprising 22 women with minimal/mild endometriosis and 23 controls found higher values of Lactate, 3-Hydroxybutyrate, L-Alanine, Glycerophosphatidylcholine, L-Valine, L-Leucine, L-Threonine, 2-Hydroxybutyrate, L-Lysine, Succinic acid in the endometriosis group and lower values of Glucose, L-Isoleucine, and L-Arginine [94].”

What the sources say

• Not checked yetcites [94] source

In the paper

“Since 2010, only 11% of reported endometriosis biomarker studies were urine-based [99].”

What the sources say

• Not checked yetcites [99] source

In the paper

“No consensus exists on changes in steroid hormone levels [23].”

What the sources say

• Not checked yetcites [23] source

In the paper

“Likewise, specific antibodies against carbonic anhydrase, transferrin, α2-HS glycoprotein, lipid peroxide modified rabbit serum albumin, copper oxidized low-density lipoprotein and malondialdehyde-modified low-density lipoprotein, laminin-I, and cardiolipin have shown promise as potential endometriosis biomarkers [23].”

What the sources say

• Not checked yetcites [23] source

In the paper

“Autoantibodies against different epitopes of tropomyosin 3 (TPM3), stomatin-like protein 2 (SLP2), and tropomodulin 3 (TMOD3) were significantly elevated in the serum of endometriosis patients with both minimal/mild and moderate/severe disease [80].”

What the sources say

• Not checked yetcites [80] source

In the paper

“Despite these contrasting results, a recent study proposing a panel of biomarkers included VEGF in two panels to detect minimal/mild endometriosis with 80% sensitivity [24].”

What the sources say

• Not checked yetcites [24] source

In the paper

“Other growth factors, such as soluble epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) have been investigated, but no difference was found between endometriosis patients and control women [23].”

What the sources say

• Not checked yetcites [23] source

In the paper

“In another study, danazol treatment of endometriosis patients resulted in an increased VEGF concentration in plasma [70].”

What the sources say

• Not checked yetcites [70] source

In the paper

“leading to the conclusion that circulating cell-free DNA may be a potential biomarker for endometriosis [95].”

What the sources say

• Not checked yetcites [95] source

In the paper

“Stearic acid was significantly reduced (P = 0.030) in endometriosis patients (n = 64) compared with controls (n = 74) [92].”

What the sources say

• Not checked yetcites [92] source

In the paper

“Furthermore, this combination of peptide peaks was validated in an independent cohort, showing a sensitivity of 89.3% and a specificity of 90% [90].”

What the sources say

• Not checked yetcites [90] source

In the paper

“In a study by Zachariah et al., the concentration of circulating cell-free nuclear DNA was higher in endometriosis patients compared with the control group (P = 0.046), leading to the conclusion that circulating cell-free DNA may be a potential biomarker for endometriosis [95].”

What the sources say

• Not checked yetcites [95] source

In the paper

“A proteomic fingerprint model, based on three peptide peaks, had 91.4% sensitivity and 95% specificity to detect endometriosis when comparing 126 patients with endometriosis with 120 healthy controls [90].”

What the sources say

• Not checked yetcites [90] source

In the paper

“Recently, a CD25high forkhead box 3+ (FOXP3+) subset of CD4+ regulatory T cells has been shown to be decreased in peripheral blood of women with endometrioma (n = 17) compared with healthy controls (n = 15) [97].”

What the sources say

• Not checked yetcites [97] source

In the paper

“A range of cell populations, including T cells, B cells, natural killer (NK) cells, macrophages/monocytes, and polymorphonuclear neutrophils, has been compared between endometriosis patients and healthy controls [23]. However, for none of these populations the utility as an endometriosis biomarker has been proven [23, 96].”

What the sources say

• Not checked yetcites [23] source
• Not checked yetcites [96] source

In the paper

“The serum concentration of its receptor, c-Met, was significantly higher in endometriosis patients (n = 130) than in controls (n = 39), in a stage dependent manner [74].”

What the sources say

• Not checked yetcites [74] source

In the paper

“The combination of hydroxysphingomyelin C16:1 and the ratio between phosphatidylcholine C36:2 to ether-phospholipid C34:2, adjusted for the effect of age and BMI, provided a sensitivity of 90.0% and a specificity of 84.3% for the detection of endometriosis [93].”

What the sources say

• Not checked yetcites [93] source

In the paper

“A combination of 5 peptide peaks, discovered by surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry, detected endometriosis with a sensitivity of 88% and a specificity of 84% in the menstrual phase [91].”

What the sources say

• Not checked yetcites [91] 2012, Obstetrics & Gynecology source

In the paper

“In patients with ovarian endometrioma, autoantibodies against Insulin-like growth factor 2 mRNA-binding protein 1 (IMP1) were significantly higher than in healthy controls [79].”

What the sources say

• Not checked yetcites [79] source

In the paper

“A study evaluating serum miRNA levels, found an elevation of miR-199a and miR-122 and a decrease of miR-145*, miR-141*, miR-542-3p, and miR-9* in endometriosis patients compared with controls [88].”

What the sources say

• Not checked yetcites [88] source

In the paper

“Using an immunoblot technique, Tokushige et al. demonstrated cytokeratin-19 (CK19) to be uniquely expressed in 11 urine samples from women with histologically proven endometriosis relative to samples from 6 women free of disease [102].”

What the sources say

• Not checked yetcites [102] source

In the paper

“Similar to peritoneal disease, ovarian endometriosis evidenced differential expression of miRNAs relative to paired eutopic endometrium in several studies [122, 123].”

What the sources say

• Not checked yetcites [122] source
• Not checked yetcites [123] source

In the paper

“and this basal cyclic variation in the endometrium must be accounted for in the interpretation of endometrial gene and protein expression signatures.”

In the paper

“A panel consisting of MMP-2, MMP-9, and MMP-9/neutrophil gealtinase-associated lipocalin was significantly elevated in a cohort of 33 women with endometriosis relative to expression in a group of 13 controls [104].”

What the sources say

• Not checked yetcites [104] source

In the paper

“Creatinine-corrected soluble fms-like tyrosine kinase (sFlt-1) was found to be significantly elevated in the urine of women with endometriosis using enzyme-linked immunosorbent assays (ELISA) [101].”

What the sources say

• Not checked yetcites [101] source

In the paper

“El-Kasti et al. identified a 3280.9 Da periovulatory peptide that differentiated all stages of endometriosis from controls with 82% senstitivity and 88% specificity.”

In the paper

“For example, the two best performing proliferative and early-secretory phase-specific disease classifiers achieved 100% accuracy using less than 100 genes for each disease classification decision.”

What the sources say

• Not checked yetcites [118] source

In the paper

“The endometrial transcriptome in women with endometriosis may have shared patterns of dysregulation with other inflammatory conditions such as hydrosalpinx [110] or other estrogen dependent diseases such as leiomyomata, endometrial polyps, or adenomyosis [111, 112].”

What the sources say

• Not checked yetcites [110] source
• Not checked yetcites [111] 2000, Journal of Clinical Endocrinology and Metabolism
• Not checked yetcites [112] source

In the paper

“At the transcript level, significant differences in gene expression exist in eutopic endometrium from women with versus without endometriosis [114–117].”

What the sources say

• Not checked yetcites [114] source
• Not checked yetcites [115] source
• Not checked yetcites [116] source
• Not checked yetcites [117] source

In the paper

“Both array-based global and targeted gene expression studies [113] have identified genes and pathways that may be involved in disease pathogenesis and reveal potential candidates for the development of an endometrial-based biomarker.”

What the sources say

• Not checked yetcites [113] source

In the paper

“In addition to menstrual cycle phase, gynecologic conditions other than endometriosis have been shown to influence eutopic endometrial gene and protein expression.”

What the sources say

• Not checked yetcites [110] source
• Not checked yetcites [111] 2000, Journal of Clinical Endocrinology and Metabolism
• Not checked yetcites [112] source

In the paper

“Despite elevation in women with endometriosis, enolase-1 lacked sufficient diagnostic power as an individual analyte (sensitivity 56% and specificity 72%) in a separate study [108].”

What the sources say

• Not checked yetcites [108] source

In the paper

“Using matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS), several groups have reported differential peptide profiles in the urine of women with endometriosis relative to that of women without endometriosis at surgery [102, 106].”

What the sources say

• Not checked yetcites [102] source
• Not checked yetcites [106] source

In the paper

“Whole genome profiling of normal endometrium revealed tremendous molecular variation between samples taken from the proliferative, early-secretory, midsecretory, and late-secretory phases of the menstrual cycle [109]”

What the sources say

• Not checked yetcites [109] source

In the paper

“As individual analytes, these proteins evidenced insufficient sensitivity and specificity for use as a biomarker.”

What the sources say

• Not checked yetcites [107] source

In the paper

“Clustered pathologies may confound the interpretation of molecular measurements in the delineation of a biomarker unique to endometriosis.”

In the paper

“Using arrays probing 377 miRNAs to compare eutopic and ectopic (peritoneal) endometrium from seven women with stage II–IV endometriosis, Teague et al., detected dysregulation of 22 miRNAs, with predicted cognate mRNA targets known to be involved in endometriosis pathogenesis [121].”

What the sources say

• Not checked yetcites [121] source

In the paper

“Like the endometrial transcriptome generally, microRNA expression in normal endometrium exhibits dynamic changes across the menstrual cycle.”

What the sources say

• Not checked yetcites [119] source

In the paper

“Tokushige et al. coupled MALDI-TOF with two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to reveal 12-fold higher expression of five proteins in affected women.”

In the paper

“A larger prospective study was subsequently unable to confirm the diagnostic potential for urinary CK19 [103], possibly due to different specimen collection techniques or different subject characteristics.”

What the sources say

• Not checked yetcites [103] source

In the paper

“Cho et al. used 2D-PAGE and tandem MS to identify significantly higher levels of 22 urine proteins in women with endometriosis including vitamin D-binding protein, prealbumin, enolase-1, and alpha1-antitrypsin [107].”

What the sources say

• Not checked yetcites [107] source

In the paper

“Global differential expression of miRNAs in eutopic compared with ectopic endometrium has been evaluated by several groups [120–124].”

What the sources say

• Not checked yetcites [120] source
• Not checked yetcites [121] source
• Not checked yetcites [122] source
• Not checked yetcites [123] source
• Not checked yetcites [124] source

In the paper

“Pan et al. identified differential expression of 48 miRNAs in a microarray analysis of early to mid-secretory eutopic endometrial tissues from endometriosis-free volunteers (n = 4), and from eutopic (n = 4) and ectopic (n = 8) endometrial tissues from women with endometriosis.”

In the paper

“Interestingly, relatively few genes were required to delineate endometriosis from other benign pelvic conditions and to classify disease severity.”

What the sources say

• Not checked yetcites [118] source

In the paper

“These highly informative gene sets provide a finite panel for biomarker development purposes.”

In the paper

“Analysis of pooled urine from healthy men and women revealed that 70% of the urine proteins originate directly from the urinary system and the remaining 30% represent proteins from other organ systems filtered by the kidney [100].”

What the sources say

• Not checked yetcites [100] source

In the paper

“A comparison of miRNA array based profiles of human primary epithelial cells isolated from estrogen-dominant late proliferative (n = 4) and progesterone-dominant mid secretory (n = 4) phase endometrial specimens identified 24 differentially expressed miRNAs [119].”

What the sources say

• Not checked yetcites [119] source

In the paper

“To date, none of the differentially expressed peptide peaks have been validated in an independent study cohort to which investigators are blinded as to patients' disease status.”

In the paper

“Wang et al. performed proteomic profiling of endometrium from 13 women with and 13 women without endometriosis identifying five differentially expressed peptide peaks (5.385 m/z, 5.425 m/z, 5.891 m/z, 6.448 m/z, and 6.898 m/z) that collectively showed 91.7% sensitivity and 90% specificity in the diagnosis of endometriosis [132].”

What the sources say

• Not checked yetcites [132] source

In the paper

“Though strengthened by the stringency of including only surgically documented presence or absence of advanced stage endometriosis, the study is limited by inclusion of control endometrium from women with coexisting intramural leiomyomata which could confound delineation of endometriosis-specific miRNA differences.”

What the sources say

• Not checked yetcites [125] source

In the paper

“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].”

What the sources say

• Not checked yetcites [132] source
• Not checked yetcites [135] source

In the paper

“In contrast to studies comparing miRNA expression in eutopic versus ectopic endometrium, relatively few studies have compared miRNA expression in eutopic endometrium from women with and without surgically confirmed endometriosis [120, 125, 126].”

What the sources say

• Not checked yetcites [120] source
• Not checked yetcites [125] source
• Not checked yetcites [126] source

In the paper

“In the largest study to date involving a total of 53 endometrial samples, a panel of three differentially expressed peptide peaks (16.069 m/z, 15.334 m/z, and 15.128 m/z) diagnosed endometriosis (all rAFS stages) with 87.5% sensitivity and 86.2% specificity [135].”

What the sources say

• Not checked yetcites [135] source

In the paper

“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].”

What the sources say

• Not checked yetcites [131] source

In the paper

“In a double blind study of endometrial pipelle samples from 99 consecutive women undergoing laparoscopy for pelvic pain and/or infertility, immunohistochemical detection of PGP9.5 demonstrated 98% sensitivity and 83% specificity for the finding of endometriosis at surgery [140].”

What the sources say

• Not checked yetcites [140] source

In the paper

“Immunohistochemical detection of the protein gene product 9.5 (PGP9.5), a highly specific pan-neuronal marker, was described at peritoneal lesions developing from surgically transplanted uterine horn segments in a rat model of endometriosis [138].”

What the sources say

• Not checked yetcites [138] source

In the paper

“In 2006, the first of these reports described reduced expression of a protein peak in secretory phase endometrium from women with mild endometriosis relative to controls [133].”

What the sources say

• Not checked yetcites [133] source

In the paper

“The overexpression of these miRNAs correlated with the downregulation of HOXA10 in endometrium from women with endometriosis.”

What the sources say

• Not checked yetcites [127] source

In the paper

“Nonetheless, the detection of nerve fibers in 29% of women without endometriosis raised concerns regarding the assay's specificity [143].”

What the sources say

• Not checked yetcites [143] source

In the paper

“For example, miR-135a (proliferative phase) and miR-135b (proliferative and secretory phases) were investigated due to their predicted interaction with Homeobox protein (HOX) A10 [127].”

What the sources say

• Not checked yetcites [127] source

In the paper

“The demonstration of aberrant microRNA expression profiles in the eutopic endometrium from women with endometriosis may yield promising biomarker targets.”

In the paper

“This can allow researchers to overcome the main pitfalls in the study design and methodology such as small sample size, lack of relevant clinical information inconsistency in sample handling and storage, and technical control of preanalytical sample variability, which contribute to controversial study results in endometriosis research [17].”

What the sources say

• Not checked yetcites [17] source

In the paper

“Importantly, nerve fibers were not observed in other benign gynecologic conditions to include endometritis, leiomyomata, or endometrial polyps.”

What the sources say

• Not checked yetcites [140] source

In the paper

“However, the adoption of this method in a clinical laboratory failed to recapitulate the accuracy of endometrial PGP9.5 immunohistochemistry in the diagnosis of women with endometriosis [143].”

What the sources say

• Not checked yetcites [143] source

In the paper

“In a parallel miRNA-mRNA array based comparison of three control early secretory phase endometrium (n = 3) with endometria from four women with moderate-severe endometriosis, six downregulated endometriosis associated miRNA were identified from the miR-9 and miR-34 miRNA families [125].”

What the sources say

• Not checked yetcites [125] source

In the paper

“These results were confirmed in a study of 27 prospectively collected eutopic endometrial specimens using identical sampling and detection methods [142].”

What the sources say

• Not checked yetcites [142] source

In the paper

“A larger study identified differential expression of 32 peptide peaks in secretory phase endometrium from 10 women with endometriosis (all rAFS stages) compared to that of 6 healthy women [134].”

What the sources say

• Not checked yetcites [134] source

In the paper

“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].”

What the sources say

• Not checked yetcites [131] source
• Not checked yetcites [132] source

In the paper

“Though the differentially expressed m/z peaks identified among separate groups showed no overlap, important methodological differences are apparent.”

In the paper

“Direct regulation of HOXA10 by miR-135a/b was subsequently confirmed by luciferase assay in cultured endometrial stromal cells.”

In the paper

“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].”

What the sources say

• Not checked yetcites [131] source

In the paper

“Despite the plethora of studies on endometriosis biomarkers, neither a single biomarker nor a panel of biomarkers has been validated for a noninvasive diagnostic test with sufficient sensitivity and specificity [17].”

What the sources say

• Not checked yetcites [17] source

In the paper

“A first step toward validation of biomarkers has been made [24, 140]; however, further studies are needed to develop a clinically useful test.”

What the sources say

• Not checked yetcites [24] source
• Not checked yetcites [140] source

In the paper

“Currently, biomarker research in endometriosis is still lacking reproducible data with high sensitivity and specificity.”

In the paper

“In addition, limitations derive from small sample size and suboptimal characterisation of specimens (no breakdown according to menstrual phase or lesion phenotype).”