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VOLUME 15 , ISSUE 2 ( March-April, 2023 ) > List of Articles

Original Article

Epigenetic vs Proteomic Biomarkers in Preterm Prediction: A Prospective Study

Chandana Mavinakere Puttaraju, Moorkoth Prasannan Anantha Sailakshmi, Nagarathnamma Rangaiah, Hanumantha Rao Hogalagere Madhava Rao, Prabhakara Somanna, Revathi Sampath

Keywords : Alpha-fetoprotein, Biomarker, Interleukin-6, MicroRNA, Preterm labor

Citation Information : Puttaraju CM, Sailakshmi MP, Rangaiah N, Rao HR, Somanna P, Sampath R. Epigenetic vs Proteomic Biomarkers in Preterm Prediction: A Prospective Study. J South Asian Feder Obs Gynae 2023; 15 (2):168-172.

DOI: 10.5005/jp-journals-10006-2206

License: CC BY-NC 4.0

Published Online: 11-05-2023

Copyright Statement:  Copyright © 2023; The Author(s).


Abstract

Background: Preterm birth (PTB) forms the prime etiology of mortality and morbidity in neonates worldwide. Our study compares serum epigenetic [microRNA-miRNA:150-5p, 223-3p, 302b-3p, 548ai] and proteomic profiling [interleukin-6 (IL-6), alpha-fetoprotein (AFP)] in prediction of preterm birth. Materials and methods: Blood was drawn from 88 pregnant women at 19–26 weeks of gestation who were followed until delivery. The concentrations of miR-150-5p, miR-223-3p, miR-302b-3p, and miR-548ai (Real-time polymerase chain reaction-RT-PCR) were compared with IL-6 and AFP [enzyme-linked immunosorbent assay (ELISA)]. Results: Our study had 75 term and 13 preterm deliveries. A “p” value of 0.003 for birth weight and preterm delivery; statistically noteworthy was appreciated. Upregulation of miR-150-5p, miR-223-3p, miR-302b-3p was seen in preterm patients with p-value of 0.021, 0.060, and 0.062, respectively. The area under the ROC curve (AUC-ROC) analysis for miR-150-5p (0.739) showed 46.15% sensitivity with 100% specificity and positive predictive value (p-value = 0.0042). miR-302b-3p had the highest sensitivity and negative predictive value of 84.6 and 96.1%, respectively. miR-223-3p defined a 100% positive predictive value and specificity. miR-548ai had 69.23% sensitivity, 44% specificity and p-value = 0.6884 (AUC-ROC). The IL-6 and AFP levels were not significantly different between two delivery groups (p-value = 0.466 and 0.399). Conclusion: miR-150-5p is an effective epigenetic biomarker for prediction of preterm labor compared to IL-6 and AFP. miR-223-3p, miR 302b-3p levels are upregulated in preterm women.

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  1. Howson CP, Kinney MV, McDougall L, et al. Born Too Soon Preterm Birth Action Group. Born too soon: preterm birth matters. Reprod Health. 2013;10 Suppl 1(Suppl 1):S1. DOI: 10.1186/1742-4755-10-S1-S1. Epub 2013 Nov 15.
  2. Chawanpaiboon S, Vogel JP, Moller A-B, et al. Global, regional, and national estimates of levels of preterm birth in 2014: A systematic review and modelling analysis. Lancet Glob Health 2019;7(1):e37–e46. DOI: 10.1016/S2214-109X(18)30451-0.
  3. Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of under-5 mortality in 2000-15: An updated systematic analysis with implications for the sustainable development goals. Lancet 2016;388(10063):3027–3035. DOI: 10.1016/S0140-6736(16)31593-8.
  4. Liu L, Chu Y, Oza S, et al. National, Regional and state-level all-cause and cause-specific under-5 mortality in India in 2000-15: a systematic analysis with implications for the Sustainable Development Goals. Lancet Glob Health. 2019 Jun;7(6): e721-e734. DOI: 10.1016/S2214-109X (19)30080-4.
  5. Gray C, McCowan LM, Patel R, et al. Maternal plasma miRNAs as biomarkers during mid-pregnancy to predict later spontaneous preterm birth: A pilot study. Sci Rep 2017;7(1):815. DOI: 10.1038/s41598-017-00713-8.
  6. Slattery MM, Morrison JJ. Preterm delivery. Lancet 2002;360(9344):1489–1497. DOI: 10.1016/S0140-6736(02)11476-0.
  7. Nanavati MS, Desai SV, Lakhani PD, et al. Role of cervical length as predictor of preterm labor and a comparison of transabdominal versus transvaginal ultrasound in determining the accuracy of cervical length. J South Asian Fed Obstet Gynaecol 2012;2(2):129–131. DOI: 10.5005/jp-journals-10006-1080.
  8. Dhumale H, Bellad MB, Shravage JC. Preterm labor: A review. J South Asian Fed Obstet Gynaecol 2011;1(3):1–4. DOI: 10.5005/jp-journals-10006-1001.
  9. He L, Hannon GJ. MicroRNAs: Small RNAs with a big role in gene regulation. Nat Rev Genet 2004;5(7):522–531. DOI: 10.1038/nrg1379.
  10. Lu J, Clark AG. Impact of microRNA regulation on variation in human gene expression. Genome Res 2012;22(7):1243–1254. DOI: 10.1101/gr.132514.111.
  11. Chim SS, Lee WS, Ting YH, et al. Systematic identification of spontaneous preterm birth-associated RNA transcripts in maternal plasma. PLoS One 2012;7(4): e34328. DOI: 10.1371/journal.pone.0034328.
  12. Correia CN, Nalpas NC, McLoughlin KE, et al. Circulating microRNAs as potential biomarkers of infectious disease. Front Immunol 2017; 8:118. DOI: 10.3389/fimmu.2017.00118.
  13. Chang RM, Xiao S, Lei X, et al. miRNA-487a promotes proliferation and metastasis in hepatocellular carcinoma. Clin Cancer Res 2017;23(10):2593–2604. DOI: 10.1158/1078-0432.CCR-16-0851.
  14. Elovitz MA, Brown AG, Anton L, et al. Distinct cervical microRNA profiles are present in women destined to have a preterm birth. Am J Obstet Gynecol 2014;210(3):221.e1–11. DOI: 10.1016/j.ajog.2013.12.043.
  15. Sanders AP, Burris HH, Just AC, et al. microRNA expression in the cervix during pregnancy is associated with length of gestation. Epigenetics 2015;10(3):221–228. DOI: 10.1080/15592294.2015.1006498.
  16. Cook J, Bennett PR, Kim SH, et al. First trimester circulating MicroRNA biomarkers predictive of subsequent preterm delivery and cervical shortening. Sci Rep 2019;9(1):5861. DOI: 10.1038/s41598-019-42166-1.
  17. Winger EE, Reed JL, Ji X, et al. MicroRNAs isolated from peripheral blood in the first trimester predict spontaneous preterm birth. PLoS One 2020;15(8):e0236805. DOI: 10.1371/journal.pone.0236805.
  18. Winger EE, Reed JL, Ji X. Early first trimester peripheral blood cell microRNA predicts risk of preterm delivery in pregnant women: Proof of concept. PLoS One 2017;12(7):e0180124. DOI: 10.1371/journal.pone.0180124.
  19. Sayed D, Abdellatif M. MicroRNAs in development and disease. Physiol Rev 2011;91(3):827–887. DOI: 10.1152/physrev.00006.2010.
  20. Wang N, Zhou Z, Wu T, et al. TNF-α-induced NF-κB activation upregulates microRNA-150-3p and inhibits osteogenesis of mesenchymal stem cells by targeting β-catenin. Open Biol 2016;6(3):150258. DOI: 10.1098/rsob.150258.
  21. Lindström TM, Bennett PR. The role of nuclear factor kappa B in human labour. Reproduction 2005;130(5):569–581. DOI: 10.1530/rep.1.00197.
  22. Schmidt WM, Spiel AO, Jilma B, et al. In vivo profile of the human leukocyte microRNA response to endotoxemia. Biochem Biophys Res Commun 2009;380(3):437–441. DOI: 10.1016/j.bbrc.2008.12.190.
  23. Sakr M, Takino T, Sabit H, et al. miR-150-5p and miR-133a suppress glioma cell proliferation and migration through targeting membrane-type-1 matrix metalloproteinase. Gene 2016;587(2):155–162. DOI: 10.1016/j.gene.2016.04.058.
  24. Fulci V, Scappucci G, Sebastiani GD, et al. miR-223 is overexpressed in T-lymphocytes of patients affected by rheumatoid arthritis. Hum Immunol 2010;71(2):206–211. DOI: 10.1016/j.humimm.2009.11.008.
  25. Haneklaus M, Gerlic M, O’Neill LA, et al. miR-223: Infection, inflammation and cancer. J Intern Med 2013;274(3):215–226. DOI: 10.1111/joim.12099.
  26. Enquobahrie DA, Hensley M, Qiu C, et al. Candidate gene and MicroRNA expression in fetal membranes and preterm delivery risk. Reprod Sci 2016;23(6):731–737. DOI: 10.1177/1933719115612925.
  27. Menon R, Debnath C, Lai A, et al. Circulating exosomal miRNA profile during term and preterm birth pregnancies: A longitudinal study. Endocrinology 2019;160(2):249–275. DOI: 10.1210/en.2018-00836.
  28. Hassan SS, Romero R, Pineles B, et al. MicroRNA expression profiling of the human uterine cervix after term labor and delivery. Am J Obstet Gynecol 2010;202(1):80.e1–e8. DOI: 10.1016/j.ajog.2009.08.016.
  29. Son GH, Kim Y, Lee JJ, et al. MicroRNA-548 regulates high mobility group box 1 expression in patients with preterm birth and chorioamnionitis. Sci Rep 2019;9(1):19746. DOI: 10.1038/s41598-019-56327-9.
  30. Wei SQ, Fraser W, Luo Z-C. Inflammatory cytokines and spontaneous preterm birth in asymptomatic women: A systematic review. Obstet Gynecol 2010;116(2 Pt 1):393–401. DOI: 10.1097/AOG.0b013e3181e6dbc0.
  31. Yuan W, Chen L, Bernal AL. Is elevated maternal serum alpha-fetoprotein in the second trimester of pregnancy associated with increased preterm birth risk? A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol 2009;145(1):57–64. DOI: 10.1016/j.ejogrb.2009.04.017.
  32. Wang X, Chen Y, Kuang H, et al. Associations between maternal AFP and β-HCG and preterm birth. Am J Perinatol 2019;36(14):1459–1463. DOI: 10.1055/s-0038-1677017.
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