Update on Biomarkers for the Detection of Endometriosis

In the paper

“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].”

What the sources say

• Not checked yetcites [42] source

In the paper

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

What the sources say

• Not checked yetcites [37] source
• Not checked yetcites [38] source

In the paper

“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.”

What the sources say

• Not checked yetcites [23] source

In the paper

“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]”

What the sources say

• Not checked yetcites [11] source
• Not checked yetcites [21] source

In the paper

“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

“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.”

What the sources say

• Not checked yetcites [24] source

In the paper

“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].”

What the sources say

• Not checked yetcites [29] source

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [41] source

In the paper

“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 [”

What the sources say

• Not checked yetcites [12] source

In the paper

“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].”

What the sources say

• Not checked yetcites [23] source

In the paper

“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.”

What the sources say

• Not checked yetcites [34] source
• Not checked yetcites [35] source
• Not checked yetcites [39] source

In the paper

“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].”

What the sources say

• Not checked yetcites [45] source

In the paper

“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].”

What the sources say

• Not checked yetcites [47] source

In the paper

“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].”

What the sources say

• Not checked yetcites [23] source
• Not checked yetcites [43] source

In the paper

“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].”

What the sources say

• Not checked yetcites [53] source

In the paper

“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].”

What the sources say

• Not checked yetcites [54] source

In the paper

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

What the sources say

• Not checked yetcites [45] source

In the paper

“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].”

What the sources say

• Not checked yetcites [24] source

In the paper

“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].”

What the sources say

• Not checked yetcites [71] source

In the paper

“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].”

What the sources say

• Not checked yetcites [23] source
• Not checked yetcites [75] source
• Not checked yetcites [76] source

In the paper

“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].”

What the sources say

• Not checked yetcites [23] source

In the paper

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

What the sources say

• Not checked yetcites [77] source
• Not checked yetcites [78] source

In the paper

“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].”

What the sources say

• Not checked yetcites [72] 2003, Di Yi Jun Yi Da Xue Xue Bao
• Not checked yetcites [23] source
• Not checked yetcites [73] source

In the paper

“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].”

What the sources say

• Not checked yetcites [98] source

In the paper

“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].”

What the sources say

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

In the paper

“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.”

What the sources say

• Not checked yetcites [86] source
• Not checked yetcites [87] source

In the paper

“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].”

What the sources say

• Not checked yetcites [23] source

In the paper

“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.”

In the paper

“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.”

In the paper

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

What the sources say

• Not checked yetcites [105] source

In the paper

“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].”

What the sources say

• Not checked yetcites [113] source

In the paper

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

What the sources say

• Not checked yetcites [109] source

In the paper

“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].”

What the sources say

• Not checked yetcites [105] source

In the paper

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

In the paper

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

What the sources say

• Not checked yetcites [121] source

In the paper

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

What the sources say

• Not checked yetcites [137] source

In the paper

“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.”

What the sources say

• Not checked yetcites [143] source

In the paper

“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].”

What the sources say

• Not checked yetcites [126] source

In the paper

“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.”

In the paper

“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].”

What the sources say

• Not checked yetcites [128] source
• Not checked yetcites [129] source
• Not checked yetcites [130] source

In the paper

“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].”

What the sources say

• Not checked yetcites [144] source

In the paper

“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].”

What the sources say

• Not checked yetcites [17] source
• Not checked yetcites [113] source
• Not checked yetcites [148] source

In the paper

“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].”

What the sources say

• Not checked yetcites [124] source

In the paper

“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].”

What the sources say

• Not checked yetcites [145] source
• Not checked yetcites [146] source
• Not checked yetcites [147] source

In the paper

“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].”

What the sources say

• Not checked yetcites [139] source

In the paper

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

In the paper

“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.”

What the sources say

• Not checked yetcites [128] source
• Not checked yetcites [130] source

In the paper

“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].”

What the sources say

• Not checked yetcites [146] source
• Not checked yetcites [147] source
• Not checked yetcites [149] source
• Not checked yetcites [150] source