Serum galectin-9 as a noninvasive biomarker for the detection of endometriosis and pelvic pain or infertility-related gynecologic disorders

Brubel, Réka; Bokor, Attila; Pohl, Ákos; Schilli, Gabriella; Szereday, László; Bacher-Szamuel, Reka; Rigó, János; Polgar, Beata

doi:10.1016/j.fertnstert.2017.09.008

Cited by 26 publications

(49 citation statements)

References 51 publications

(52 reference statements)

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“…However, surgery is a highly invasive procedure with potential risks. Although several studies have found several biomarkers in endometriosis, a definite diagnostic biomarker is not yet available [4,5].…”

Section: Introductionmentioning

confidence: 99%

Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

Zhang

Yuan

et al. 2020

Disease Markers

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Background. A reliable noninvasive biomarker is not yet available for endometriosis diagnosis. Novel biomarkers for the diagnosis of endometriosis are urgently needed. The molecular constituents of exosomes, especially exosomal microRNAs (miRNAs), have considerable potential as novel biomarkers for clinical diagnosis. This study is aimed at exploring aberrant exosomal miRNA profiles by using miRNA microarray and at providing more accurate molecular biomarkers of endometriosis. Methods. Exosomes were isolated from the serum of patients with endometriosis and negative controls and identified by electron microscopy, nanoparticle tracking analysis, and Western blot. Exosomal miRNAs were profiled by miRNA microarrays. The expression of selective serum exosomal miRNA was validated by qRT-PCR. Receiver operating characteristic (ROC) curves were established to explore the diagnostic value of selective miRNAs. Finally, GO annotation and KEGG pathway enrichment analyses were used to display possible functions associated with the two miRNAs. Results. A total of 24 miRNAs showed differential levels of enrichment with P<0.05 and log2 fold change>1 by miRNA microarrays. Among the six selective miRNAs (i.e., miR-134-5p, miR-197-5p, miR-22-3p, miR-320a, miR-494-3p, and miR-939-5p), qRT-PCR analysis revealed that miR-22-3p and miR-320a were significantly upregulated in serum exosomes from patients with endometriosis compared with negative individuals. ROC curve revealed that the serum exosomal miR-22-3p and miR-320a yielded the area under the curve values of 0.855 and 0.827, respectively. Conclusion. Our results demonstrated that exosomal miR-22-3p and miR-320a were significantly increased in the sera of patients with endometriosis. The two miRNAs may be useful potential biomarkers for endometriosis diagnosis.

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Section: Introductionmentioning

confidence: 99%

Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

Zhang

Yuan

et al. 2020

Disease Markers

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“…It affects 6%–10% of women of reproductive age (Burney and Giudice, 2012; Laux-Biehlmann et al, 2015). The common symptoms of endometriosis are pain and subfertility (Brubel et al, 2017; Righarts et al, 2018). Pain symptoms associated with endometriosis include dysmenorrhea, dyspareunia, dysuria, dyschezia, and chronic pelvic pain, which profoundly affect quality of life (Simoens et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Fractalkine/CX3CR1 Contributes to Endometriosis-Induced Neuropathic Pain and Mechanical Hypersensitivity in Rats

Liu

Chen

Qiu

et al. 2018

Front. Cell. Neurosci.

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Pain is the most severe and common symptom of endometriosis. Its underlying pathogenetic mechanism is poorly understood. Nerve sensitization is a particular research challenge, due to the limitations of general endometriosis models and sampling nerve tissue from patients. The chemokine fractalkine (FKN) has been demonstrated to play a key role in various forms of neuropathic pain, while its role in endometriotic pain is unknown. Our study was designed to explore the function of FKN in the development and maintenance of peripheral hyperalgesia and central sensitization in endometriosis using a novel endometriosis animal model developed in our laboratory. After modeling, behavioral tests were carried out and the optimal time for molecular changes was obtained. We extracted ectopic tissues and L4–6 spinal cords to detect peripheral and central roles for FKN, respectively. To assess morphologic characteristics of endometriosis-like lesions—as well as expression and location of FKN/CX3CR1—we performed H&E staining, immunostaining, and western blotting analyses. Furthermore, inhibition of FKN expression in the spinal cord was achieved by intrathecal administration of an FKN-neutralizing antibody to demonstrate its function. Our results showed that implanted autologous uterine tissue around the sciatic nerve induced endometriosis-like lesions and produced mechanical hyperalgesia and allodynia. FKN was highly expressed on macrophages, whereas its receptor CX3CR1 was overexpressed in the myelin sheath of sciatic nerve fibers. Overexpressed FKN was also observed in neurons. CX3CR1/pp38-MAPK was upregulated in activated microglia in the spinal dorsal horn. Intrathecal administration of FKN-neutralizing antibody not only reversed the established mechanical hyperalgesia and allodynia, but also inhibited the expression of CX3CR1/pp38-MAPK in activated microglia, which was essential for the persistence of central sensitization. We concluded that the FKN/CX3CR1 signaling pathway might be one of the mechanisms of peripheral hyperalgesia in endometriosis, which requires further studies. Spinal FKN is important for the development and maintenance of central sensitization in endometriosis, and it may further serve as a novel therapeutic target to relieve persistent pain associated with endometriosis.

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“…Using a GalPharma (GalP) ELISA, we have reported that the concentration of Gal-9 in the blood fluctuates rapidly, reflecting the pathological conditions of patients with various diseases [8][9][10][11][12][13][14][15][16][17]. Similar disease-related fluctuations have been reported using both independently developed and commercially produced ELISAs [18][19][20][21][22][23][24][25][26][27][28][29][30][31]. When the reported Gal-9 concentrations were compared, a large divergence was observed in the results, even within healthy control groups, with values ranging from 0 to 26, 560 pg/mL.…”

Section: Introductionmentioning

confidence: 54%

Plasma Galectin-9 Concentrations in Normal and Diseased Condition

Niki

Fujita

Rosen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Galectin-9 is a soluble immune modulator with versatile functions, including a role as an immune checkpoint molecule. Therefore, the amount of galectin-9 in the blood may reflect an individual’s immunological balance. Many studies have conducted galectin-9 measurements; however, the reported galectin-9 concentration in the blood varies greatly, even within healthy controls. This study investigates the variation between the reported and actual concentrations of galectin-9. Methods: A GalPharma ELISA and an R&D Systems ELISA kit were directly compared using the same set of plasma and a series of recombinant galectins, including degraded galectin-9. Furthermore, galectin-9 in plasma was concentrated using anti-galectin-9 antibody-conjugated beads, and subjected to western blotting to estimate the quantity and integrity of galectin-9 and assess the consistency of ELISA measurements. Results: The R&D Systems’ ELISA indicated a 50-fold higher median concentration of plasma galectin-9 than that indicated by the GalPharma ELISA. This variation is due to aberrantly enhanced reactivity of the R&D Systems’ ELISA to degraded galectin-9 present in small quantities in the plasma. The GalPharma ELISA could detect only intact galectin-9 and its results correlated well with the plasma galectin-9 level obtained by western blotting. Conclusion: ELISA kits from R&D Systems reacts aberrantly higher against degraded galectin-9 than the intact galectin-9. Therefore, the existence of a small amount of degraded galectin-9 in a test sample hinders the quantification. As galectin-9 is a fragile protein, this is a serious concern when using this kit. Based on quantifications from the GalPharma ELISA, the median (25^th-75^th percentiles) galectin-9 concentration in healthy subjects in the current study cohort was calculated as 110 pg/mL (67 -154 pg/mL).

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Serum galectin-9 as a noninvasive biomarker for the detection of endometriosis and pelvic pain or infertility-related gynecologic disorders

Abstract: Our results suggest that Gal-9 could be a promising noninvasive biomarker of endometriosis and a predictor of various infertility or pelvic pain-related gynecologic disorders.

Cited by 26 publications

References 51 publications

Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

Serum Exosomal MicroRNAs as Potential Circulating Biomarkers for Endometriosis

Fractalkine/CX3CR1 Contributes to Endometriosis-Induced Neuropathic Pain and Mechanical Hypersensitivity in Rats

Plasma Galectin-9 Concentrations in Normal and Diseased Condition

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