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miR-424-5p combined with miR-17-5p has high diagnostic efficacy for endometriosis

  • General Gynecology
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Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Endometriosis (EMT) is a chronic benign disease with high prevalence. This study investigated the diagnostic value of serum miR-17-5p, miR-424-5p, and their combined expressions for EMT.

Methods

Total 80 EMT patients of reproductive age who underwent laparoscopy or laparotomy and were confirmed by pathological examination were included as the study subjects, and another 80 healthy women of reproductive age receiving gynecological examination and ultrasonography with no pelvic abnormalities were selected as the control group. The whole blood samples of enrolled subjects were collected and clinical characteristics were recorded. The miR-17-5p, miR-424-5p, VEGFA, IL-4, and IL-6 levels in the serum were measured. ROC curve was used to evaluate the diagnostic efficacy of miR-17-5p and miR-424-5p expressions for EMT. Pearson correlation was performed to analyze the correlation of miR-17-5p and miR-424-5p with clinical indexes in EMT patients.

Results

miR-17-5p and miR-424-5p were downregulated in EMT patients. For diagnosing EMT, the AUC of miR-17-5p was 0.865 and cutoff value was 0.890 (91.3% sensitivity and 85% specificity), the AUC of miR-424-5p was 0.737, and cutoff value was 0.915 (98.8% sensitivity and 61.2% specificity), and the AUC of miR-424-5p combined with miR-17-5p was 0.938 and cutoff value was 2.205 (93.8% sensitivity and 88.7% specificity), with the diagnostic efficacy higher than miR-424-5p or miR-17-5p alone. miR-17-5p and miR-424-5p expressions were negatively correlated with dysmenorrhea, infertility, pelvic pain, and rASRM stage, but not with age, BMI, menstrual disorder, and nulliparity. VEGFA, IL-4, IL-6, and CA-125 were increased in EMT patients and were inversely associated with miR-17-5p and miR-424-5p.

Conclusion

miR-424-5p combined with miR-17-5p has high diagnostic efficacy for EMT.

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References

  1. Garcia-Ibanez P, Yepes-Molina L, Ruiz-Alcaraz AJ, Martinez-Esparza M, Moreno DA, Carvajal M, Garcia-Penarrubia P (2020) Brassica bioactives could ameliorate the chronic inflammatory condition of endometriosis. Int J Mol Sci. https://doi.org/10.3390/ijms21249397

    Article  Google Scholar 

  2. Golabek A, Kowalska K, Olejnik A (2021) Polyphenols as a diet therapy concept for endometriosis-current opinion and future perspectives. Nutrients. https://doi.org/10.3390/nu13041347

    Article  Google Scholar 

  3. Anastasiu CV, Moga MA, Elena Neculau A, Balan A, Scarneciu I, Dragomir RM, Dull AM, Chicea LM (2020) Biomarkers for the noninvasive diagnosis of endometriosis: state of the art and future perspectives. Int J Mol Sci. https://doi.org/10.3390/ijms21051750

    Article  Google Scholar 

  4. Wang D, Yang Q, Wang H, Liu C (2021) Malignant transformation of hepatic endometriosis: a case report and literature review. BMC Womens Health 21:249. https://doi.org/10.1186/s12905-021-01366-6

    Article  Google Scholar 

  5. Hur C, Falcone T (2021) Robotic treatment of bowel endometriosis. Best Pract Res Clin Obstet Gynaecol 71:129–143. https://doi.org/10.1016/j.bpobgyn.2020.05.012

    Article  Google Scholar 

  6. Greenbaum H, Galper BL, Decter DH, Eisenberg VH (2021) Endometriosis and autoimmunity: can autoantibodies be used as a non-invasive early diagnostic tool? Autoimmun Rev 20:102795. https://doi.org/10.1016/j.autrev.2021.102795

    Article  CAS  Google Scholar 

  7. Peng C, Huang Y, Zhou Y (2021) Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis. Arch Gynecol Obstet 304:231–252. https://doi.org/10.1007/s00404-020-05900-z

    Article  CAS  Google Scholar 

  8. Samimi M, Pourhanifeh MH, Mehdizadehkashi A, Eftekhar T, Asemi Z (2019) The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: basic science and new insights based on gene expression. J Cell Physiol 234:19384–19392. https://doi.org/10.1002/jcp.28666

    Article  CAS  Google Scholar 

  9. Bjorkman S, Taylor HS (2019) MicroRNAs in endometriosis: biological function and emerging biomarker candidatesdagger. Biol Reprod 100:1135–1146. https://doi.org/10.1093/biolre/ioz014

    Article  Google Scholar 

  10. Agrawal S, Tapmeier T, Rahmioglu N, Kirtley S, Zondervan K, Becker C (2018) The miRNA Mirage: how close are we to finding a non-invasive diagnostic biomarker in endometriosis? A systematic review. Int J Mol Sci. https://doi.org/10.3390/ijms19020599

    Article  Google Scholar 

  11. Fridrich A, Hazan Y, Moran Y (2019) Too many false targets for MicroRNAs: challenges and pitfalls in prediction of miRNA targets and their gene ontology in model and non-model organisms. BioEssays 41:e1800169. https://doi.org/10.1002/bies.201800169

    Article  Google Scholar 

  12. Mirna M, Paar V, Rezar R, Topf A, Eber M, Hoppe UC, Lichtenauer M, Jung C (2019) MicroRNAs in inflammatory heart diseases and sepsis-induced cardiac dysfunction: a potential scope for the future? Cells. https://doi.org/10.3390/cells8111352

    Article  Google Scholar 

  13. Cho S, Mutlu L, Grechukhina O, Taylor HS (2015) Circulating microRNAs as potential biomarkers for endometriosis. Fertil Steril 103(1252–60):e1. https://doi.org/10.1016/j.fertnstert.2015.02.013

    Article  CAS  Google Scholar 

  14. Cosar E, Mamillapalli R, Ersoy GS, Cho S, Seifer B, Taylor HS (2016) Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array-based analysis. Fertil Steril 106:402–409. https://doi.org/10.1016/j.fertnstert.2016.04.013

    Article  CAS  Google Scholar 

  15. Huan Q, Cheng SC, Du ZH, Ma HF, Li C (2021) LncRNA AFAP1-AS1 regulates proliferation and apoptosis of endometriosis through activating STAT3/TGF-beta/Smad signaling via miR-424-5p. J Obstet Gynaecol Res 47:2394–2405. https://doi.org/10.1111/jog.14801

    Article  CAS  Google Scholar 

  16. Papari E, Noruzinia M, Kashani L, Foster WG (2020) Identification of candidate microRNA markers of endometriosis with the use of next-generation sequencing and quantitative real-time polymerase chain reaction. Fertil Steril 113:1232–1241. https://doi.org/10.1016/j.fertnstert.2020.01.026

    Article  CAS  Google Scholar 

  17. Hsu CY, Hsieh TH, Tsai CF et al (2014) miRNA-199a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis. J Pathol 232:330–343. https://doi.org/10.1002/path.4295

    Article  CAS  Google Scholar 

  18. Bourhis M, Palle J, Galy-Fauroux I, Terme M (2021) Direct and indirect modulation of T Cells by VEGF-A counteracted by anti-angiogenic treatment. Front Immunol 12:616837. https://doi.org/10.3389/fimmu.2021.616837

    Article  CAS  Google Scholar 

  19. Ma Y, Huang YX, Chen YY (2017) miRNA34a5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis. Mol Med Rep 16:8259–8264. https://doi.org/10.3892/mmr.2017.7677

    Article  CAS  Google Scholar 

  20. Braza-Boils A, Gilabert-Estelles J, Ramon LA, Gilabert J, Mari-Alexandre J, Chirivella M, Espana F, Estelles A (2013) Peritoneal fluid reduces angiogenesis-related microRNA expression in cell cultures of endometrial and endometriotic tissues from women with endometriosis. PLoS ONE 8:e62370. https://doi.org/10.1371/journal.pone.0062370

    Article  CAS  Google Scholar 

  21. Pang QX, Liu Z (2020) miR-17–5p mitigates endometriosis by directly regulating VEGFA. J Biosci 45. https://www.ncbi.nlm.nih.gov/pubmed/32515360

  22. Braza-Boils A, Mari-Alexandre J, Gilabert J, Sanchez-Izquierdo D, Espana F, Estelles A, Gilabert-Estelles J (2014) MicroRNA expression profile in endometriosis: its relation to angiogenesis and fibrinolytic factors. Hum Reprod 29:978–988. https://doi.org/10.1093/humrep/deu019

    Article  CAS  Google Scholar 

  23. Wang F, Wang H, Jin D, Zhang Y (2018) Serum miR-17, IL-4, and IL-6 levels for diagnosis of endometriosis. Medicine (Baltimore) 97:e10853. https://doi.org/10.1097/MD.0000000000010853

    Article  CAS  Google Scholar 

  24. Acien P, Shaw RW, Irvine L, Burford G, Gardner R (1989) CA 125 levels in endometriosis patients before, during and after treatment with danazol or LHRH agonists. Eur J Obstet Gynecol Reprod Biol 32:241–246. https://doi.org/10.1016/0028-2243(89)90042-7

    Article  CAS  Google Scholar 

  25. Knific T, Vouk K, Vogler A, Osredkar J, Gstottner M, Wenzl R, Rizner TL (2018) Models including serum CA-125, BMI, cyst pathology, dysmenorrhea or dyspareunia for diagnosis of endometriosis. Biomark Med 12:737–747. https://doi.org/10.2217/bmm-2017-0426

    Article  CAS  Google Scholar 

  26. Bazot M, Kermarrec E, Bendifallah S, Darai E (2021) MRI of intestinal endometriosis. Best Pract Res Clin Obstet Gynaecol 71:51–63. https://doi.org/10.1016/j.bpobgyn.2020.05.013

    Article  Google Scholar 

  27. Shan J, Ni Z, Cheng W, Zhou L, Zhai D, Sun S, Yu C (2021) Gut microbiota imbalance and its correlations with hormone and inflammatory factors in patients with stage 3/4 endometriosis. Arch Gynecol Obstet 304:1363–1373. https://doi.org/10.1007/s00404-021-06057-z

    Article  CAS  Google Scholar 

  28. Wu Y, Yuan W, Ding H, Wu X (2022) Serum exosomal miRNA from endometriosis patients correlates with disease severity. Arch Gynecol Obstet 305:117–127. https://doi.org/10.1007/s00404-021-06227-z

    Article  CAS  Google Scholar 

  29. Zhao L, Gu C, Ye M, Zhang Z, Li L, Fan W, Meng Y (2018) Integration analysis of microRNA and mRNA paired expression profiling identifies deregulated microRNA-transcription factor-gene regulatory networks in ovarian endometriosis. Reprod Biol Endocrinol 16:4. https://doi.org/10.1186/s12958-017-0319-5

    Article  CAS  Google Scholar 

  30. Pateisky P, Pils D, Szabo L, Kuessel L, Husslein H, Schmitz A, Wenzl R, Yotova I (2018) hsa-miRNA-154-5p expression in plasma of endometriosis patients is a potential diagnostic marker for the disease. Reprod Biomed Online 37:449–466. https://doi.org/10.1016/j.rbmo.2018.05.007

    Article  CAS  Google Scholar 

  31. Jia SZ, Yang Y, Lang J, Sun P, Leng J (2013) Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum Reprod 28:322–330. https://doi.org/10.1093/humrep/des413

    Article  CAS  Google Scholar 

  32. Wu J, Cui SH, Li HZ, Li QH, Yuan R, Zhang YP, Zhao TW (2016) Ultrasound diagnosis in gynecological acute abdomen. J Biol Regul Homeost Agents 30: 211–7. https://www.ncbi.nlm.nih.gov/pubmed/27049094

  33. Wang S, Yi M, Zhang X, Zhang T, Jiang L, Cao L, Zhou Y, Fang X (2021) Effects of CDKN2B-AS1 on cellular proliferation, invasion and AKT3 expression are attenuated by miR-424-5p in a model of ovarian endometriosis. Reprod Biomed Online 42:1057–1066. https://doi.org/10.1016/j.rbmo.2021.02.004

    Article  CAS  Google Scholar 

  34. Xu SL, Tian YY, Zhou Y, Liu LQ (2020) Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 93:489–498. https://doi.org/10.1111/cen.14217

    Article  CAS  Google Scholar 

  35. Wu XG, Chen JJ, Zhou HL, Wu Y, Lin F, Shi J, Wu HZ, Xiao HQ, Wang W (2021) Identification and validation of the signatures of infiltrating immune cells in the eutopic endometrium endometria of women with endometriosis. Front Immunol 12:671201. https://doi.org/10.3389/fimmu.2021.671201

    Article  CAS  Google Scholar 

  36. Knox B, Ong YC, Bakar MA, Grover SR (2019) A longitudinal study of adolescent dysmenorrhoea into adulthood. Eur J Pediatr 178:1325–1332. https://doi.org/10.1007/s00431-019-03419-3

    Article  Google Scholar 

  37. Esfandiari F, Chitsazian F, Jahromi MG, Favaedi R, Bazrgar M, Aflatoonian R, Afsharian P, Aflatoonian A, Shahhoseini M (2021) HOX cluster and their cofactors showed an altered expression pattern in eutopic and ectopic endometriosis tissues. Reprod Biol Endocrinol 19:132. https://doi.org/10.1186/s12958-021-00816-y

    Article  CAS  Google Scholar 

  38. Li J, Ren L, Li M, Yang C, Chen J, Chen Q (2021) Screening of potential key genes related to tubal factor infertility based on competitive endogenous RNA network. Genet Test Mol Biomarkers 25:325–333. https://doi.org/10.1089/gtmb.2020.0083

    Article  CAS  Google Scholar 

  39. Feng Y, Zou S, Weijdegard B, Chen J, Cong Q, Fernandez-Rodriguez J, Wang L, Billig H, Shao R (2014) The onset of human ectopic pregnancy demonstrates a differential expression of miRNAs and their cognate targets in the Fallopian tube. Int J Clin Exp Pathol 7: 64–79. https://www.ncbi.nlm.nih.gov/pubmed/24427327

  40. Karadadas E, Hortu I, Ak H, Ergenoglu AM, Karadadas N, Aydin HH (2020) Evaluation of complement system proteins C3a, C5a and C6 in patients of endometriosis. Clin Biochem 81:15–19. https://doi.org/10.1016/j.clinbiochem.2020.04.005

    Article  CAS  Google Scholar 

  41. Wei Y, Liang Y, Lin H, Dai Y, Yao S (2020) Autonomic nervous system and inflammation interaction in endometriosis-associated pain. J Neuroinflammation 17:80. https://doi.org/10.1186/s12974-020-01752-1

    Article  Google Scholar 

  42. Zhou WJ, Yang HL, Shao J, Mei J, Chang KK, Zhu R, Li MQ (2019) Anti-inflammatory cytokines in endometriosis. Cell Mol Life Sci 76:2111–2132. https://doi.org/10.1007/s00018-019-03056-x

    Article  CAS  Google Scholar 

  43. Mosbah A, Nabiel Y, Khashaba E (2016) Interleukin-6, intracellular adhesion molecule-1, and glycodelin A levels in serum and peritoneal fluid as biomarkers for endometriosis. Int J Gynaecol Obstet 134:247–251. https://doi.org/10.1016/j.ijgo.2016.01.018

    Article  CAS  Google Scholar 

  44. Korbel C, Gerstner MD, Menger MD, Laschke MW (2018) Notch signaling controls sprouting angiogenesis of endometriotic lesions. Angiogenesis 21:37–46. https://doi.org/10.1007/s10456-017-9580-7

    Article  CAS  Google Scholar 

  45. Delbandi AA, Mahmoudi M, Shervin A, Heidari S, Kolahdouz-Mohammadi R, Zarnani AH (2020) Evaluation of apoptosis and angiogenesis in ectopic and eutopic stromal cells of patients with endometriosis compared to non-endometriotic controls. BMC Womens Health 20:3. https://doi.org/10.1186/s12905-019-0865-4

    Article  CAS  Google Scholar 

  46. Hortu I, Ozceltik G, Karadadas E, Erbas O, Yigitturk G, Ulukus M (2020) The role of ankaferd blood stopper and oxytocin as potential therapeutic agents in endometriosis: a rat model. Curr Med Sci 40:556–562. https://doi.org/10.1007/s11596-020-2213-1

    Article  CAS  Google Scholar 

  47. Kokot I, Piwowar A, Jedryka M, Solkiewicz K, Kratz EM (2021) Diagnostic significance of selected serum inflammatory markers in women with advanced endometriosis. Int J Mol Sci. https://doi.org/10.3390/ijms22052295

    Article  Google Scholar 

  48. Malutan AM, Drugan C, Drugan T, Ciortea R, Mihu D (2016) The association between interleukin-4 -590C/T genetic polymorphism, IL-4 serum level, and advanced endometriosis. Cent Eur J Immunol 41:176–181. https://doi.org/10.5114/ceji.2016.60992

    Article  CAS  Google Scholar 

  49. Volpato LK, Horewicz VV, Bobinski F, Martins DF, Piovezan AP (2018) Annexin A1, FPR2/ALX, and inflammatory cytokine expression in peritoneal endometriosis. J Reprod Immunol 129:30–35. https://doi.org/10.1016/j.jri.2018.08.002

    Article  CAS  Google Scholar 

  50. Jiang J, Jiang Z, Xue M (2019) Serum and peritoneal fluid levels of interleukin-6 and interleukin-37 as biomarkers for endometriosis. Gynecol Endocrinol 35:571–575. https://doi.org/10.1080/09513590.2018.1554034

    Article  CAS  Google Scholar 

  51. Li Y, Guo W, Cai Y (2020) NEAT1 promotes LPS-induced inflammatory injury in macrophages by regulating MiR-17-5p/TLR4. Open Med (Wars) 15:38–49. https://doi.org/10.1515/med-2020-0007

    Article  CAS  Google Scholar 

  52. Li C, Zhang M, Dai Y, Xu Z (2020) MicroRNA-424-5p regulates aortic smooth muscle cell function in atherosclerosis by blocking APOC3-mediated nuclear factor-kappaB signalling pathway. Exp Physiol 105:1035–1049. https://doi.org/10.1113/EP088088

    Article  CAS  Google Scholar 

  53. Zhang YZ, Wang J, Xu F (2017) Circulating miR-29b and miR-424 as prognostic markers in patients with acute cerebral infarction. Clin Lab 63:1667–1674. https://doi.org/10.7754/Clin.Lab.2017.170420

    Article  CAS  Google Scholar 

  54. Braza-Boils A, Salloum-Asfar S, Mari-Alexandre J et al (2015) Peritoneal fluid modifies the microRNA expression profile in endometrial and endometriotic cells from women with endometriosis. Hum Reprod 30:2292–2302. https://doi.org/10.1093/humrep/dev204

    Article  CAS  Google Scholar 

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CLL is the guarantor of integrity of the entire study; CLL contributed to the study concepts, study design, definition of intellectual content, literature research, clinical studies, experimental studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing and manuscript review; SLZ contributed to the study concepts, study design, definition of intellectual content, literature research, clinical studies, data acquisition, data analysis, manuscript preparation, manuscript editing and manuscript review; MJL contributed to the study design, clinical studies, experimental studies, data acquisition, data analysis, statistical analysis, manuscript preparation, manuscript editing and manuscript review; all authors read and approved the final manuscript.

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Correspondence to Chunli Lin or Saili Zeng.

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This study was approved by the academic ethics committee of Hunan Province Maternal and Child Health care Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All participants were fully informed and voluntarily signed the informed consent before sampling.

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Lin, C., Zeng, S. & Li, M. miR-424-5p combined with miR-17-5p has high diagnostic efficacy for endometriosis. Arch Gynecol Obstet 307, 169–177 (2023). https://doi.org/10.1007/s00404-022-06492-6

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