Proteomic Profiling of Maternal Serum for Early Risk Analysis of
Preterm Birth

Javeria      Malik; Shaaf      Ahmad; Humaira      Aziz; Nabila      Roohi; Muhammad   Amir   Iqbal

doi:10.2174/1570164619666220412122959

Abstract

Background: The absence of absolute clinical indicators and suitable biomarkers hinders the timely diagnosis of women at risk of preterm birth. It influences roughly 12% of births. At delivery and clinical presentation, preterm births are generally inspected based on the gestational period. Different disturbed pathways are associated with the signs of at-risk pregnancies.

Objective: The main purpose of this study is to analyze and explore the serum proteome of early deliveries and help health care professionals to improve the understanding of the progression of preterm birth.

Methods: In the present study, 200 pregnant females of 20-30 years of age were selected. We collected samples of second and third-trimester pregnant females, out of which 40 females delivered preterm. We further divided them into three groups, i.e., extremely preterm group, very preterm, and controls. Overall comparison of serum profiles of all the three groups expressing fourteen proteins ranging between 200-10kDa was made. Serum proteins were isolated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photographed by totalLab quant software. Groups were evaluated using the ANOVA Tukey’s Post Hoc analysis.

Results: Proteins of 69kDa and 15kDa expressed a significant decrease when compared with control subjects. In contrast, the proteins of 23kDa expressed a significant increase, while the proteins of 77kDa, 45kDa, and 25kDa demonstrated no considerable variation.

Conclusion: The serum proteins showing significant difference as compared to the control group will serve as predictive biomarkers for at-risk pregnancies. The present study is expected to considerably improve the understanding of the disease pathogenesis along with improved diagnostic and therapeutic approaches leading to better management of pregnancy and reducing the risk of preterm birth.

Keywords: Preterm birth, biomarkers, gestational age, serum profiles, electrophoresis, at-risk pregnancy, early delivery.

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[1] 
D’Silva, A.M.; Hyett, J.A.; Coorssen, J.R. Proteomic analysis of first trimester maternal serum to identify candidate biomarkers potentially predictive of spontaneous preterm birth. J. Proteomics,  2018, 178, 31-42.
[http://dx.doi.org/10.1016/j.jprot.2018.02.002] [PMID: 29448056] 
[2] 
Liu, J.; Zhang, S.; Liu, M.; Wang, Q.; Shen, H.; Zhang, Y. Maternal pre-pregnancy infection with hepatitis B virus and the risk of preterm birth: A population-based cohort study. Lancet Glob. Health,  2017, 5(6), e624-e632.
[http://dx.doi.org/10.1016/S2214-109X(17)30142-0] [PMID: 28495266] 
[3] 
Lucaroni, F.; Morciano, L.; Rizzo, G.; D’ Antonio, F.; Buonuomo, E.; Palombi, L.; Arduini, D. Biomarkers for predicting spontaneous preterm birth: An umbrella systematic review. J. Matern. Fetal Neonatal Med.,  2018, 31(6), 726-734.
[http://dx.doi.org/10.1080/14767058.2017.1297404] [PMID: 28274163] 
[4] 
Kacerovsky, M.; Lenco, J.; Musilova, I.; Tambor, V.; Lamont, R.; Torloni, M.R.; Menon, R. PREBIC biomarker working group 2012-2013. Proteomic biomarkers for spontaneous preterm birth: A systematic review of the literature. Reprod. Sci.,  2014, 21(3), 283-295.
[http://dx.doi.org/10.1177/1933719113503415] [PMID: 24060632] 
[5] 
Ezrin, A.M.; Brohman, B.; Willmot, J.; Baxter, S.; Moore, K.; Luther, M.; Fannon, M.R.; Sibai, B. Circulating serum-derived microparticles provide novel proteomic biomarkers of spontaneous preterm birth. Am. J. Perinatol.,  2015, 32(6), 605-614.
[http://dx.doi.org/10.1055/s-0035-1547322] [PMID: 25825961] 
[6] 
Coorssen, J.R.; Yergey, A.L. Proteomics is analytical chemistry: Fitness-for-purpose in the application of top-down and bottom-up analyses. Proteomes,  2015, 3(4), 440-453.
[http://dx.doi.org/10.3390/proteomes3040440] [PMID: 28248279] 
[7] 
Oliveira, B.M.; Coorssen, J.R.; Martins-de-Souza, D. 2DE: the phoenix of proteomics. J. Proteomics,  2014, 104, 140-150.
[http://dx.doi.org/10.1016/j.jprot.2014.03.035] [PMID: 24704856] 
[8] 
Thiede, B.; Koehler, C.J.; Strozynski, M.; Treumann, A.; Stein, R.; Zimny-Arndt, U.; Schmid, M.; Jungblut, P.R. High resolution quantitative proteomics of HeLa cells protein species using stable isotope labeling with amino acids in cell culture(SILAC), two-dimensional gel electrophoresis(2DE) and nano-liquid chromatograpohy coupled to an LTQ-OrbitrapMass spectrometer. Mol. Cell. Proteomics,  2013, 12(2), 529-538.
[http://dx.doi.org/10.1074/mcp.M112.019372] [PMID: 23033477] 
[9] 
Quinn, J-A.; Munoz, F.M.; Gonik, B.; Frau, L.; Cutland, C.; Mallett-Moore, T.; Kissou, A.; Wittke, F.; Das, M.; Nunes, T.; Pye, S.; Watson, W.; Ramos, A.A.; Cordero, J.F.; Huang, W-T.; Kochhar, S.; Buttery, J. Preterm birth: Case definition & guidelines for data collection, analysis, and presentation of immunisation safety data. Vaccine,  2016, 34(49), 6047-6056.
[http://dx.doi.org/10.1016/j.vaccine.2016.03.045] [PMID: 27743648] 
[10] 
Beck, S.; Wojdyla, D.; Say, L.; Betran, A.P.; Merialdi, M.; Requejo, J.H.; Rubens, C.; Menon, R.; Van Look, P.F. The worldwide incidence of preterm birth: A systematic review of maternal mortality and morbidity. Bull. World Health Organ.,  2010, 88(1), 31-38.
[http://dx.doi.org/10.2471/BLT.08.062554] [PMID: 20428351] 
[11] 
Conde-Agudelo, A.; Papageorghiou, A.T.; Kennedy, S.H.; Villar, J. Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: A systematic review and meta-analysis. BJOG,  2011, 118(9), 1042-1054.
[http://dx.doi.org/10.1111/j.1471-0528.2011.02923.x] [PMID: 21401853] 
[12] 
(a) Schenk, S.; Schoenhals, G.J.; de Souza, G.; Mann, M. A high confidence, manually validated human blood plasma protein reference set. BMC Med. Genomics,  2008, 1(1), 41.
[http://dx.doi.org/10.1186/1755-8794-1-41] [PMID: 18793429] 
(b)  Vanuytsel, T.; Vermeire, S.; Cleynen, I. The role of haptoglobin
and its related protein, Zonulin, in inflammatory bowel disease.
Tissue Barriers, 2013, 1(5), e27321.
[http://dx.doi.org/10.4161/tisb.27321] [PMID: 24868498] 
(c)  Kasai, K.; Nishiyama, N.; Yamauchi, K. Characterization of Oncorhynchus
mykiss 5-hydroxyisourate hydrolase/transthyretin superfamily:
Evolutionary and functional analyses. Gene, 2013,
531(2), 326-336.
[http://dx.doi.org/10.1016/j.gene.2013.08.071] [PMID: 23994290] 
(d)  Alberts, A.; Klingberg, A.; Wessig, A.K.; Combes, C.; Witte,
T.; Brand, K.; Pich, A.; Neumann, K. C-reactive protein (CRP)
recognizes uric acid crystals and recruits proteases C1 and
MASP1. Sci. Rep., 2020, 10(1), 6391.
[http://dx.doi.org/10.1038/s41598-020-63318-8] [PMID: 32286427] 
(e)  Jugnam-Ang, W.; Pannengpetch, S.; Isarankura-Na-Ayudhya,
P.; Thippakorn, C.; Isarankura-Na-Ayudhya, C.; Lawung, R.;
Prachayasittiku, V. Retinol-binding protein 4 and its potential
roles in hypercholesterolemia revealed by proteomics. EXCLI J.,
2015, 14, 999-1013.
[http://dx.doi.org/10.17179/excli2015-478] [PMID: 27103892] 
(f)  Boldt, J. Use of albumin: an update. Br. J. Anaesth., 2010,
104(3), 276-284.
[http://dx.doi.org/10.1093/bja/aep393] [PMID: 20100698] 
(g)  Gundry, R.L.; Fu, Q.; Jelinek, C.A.; Van Eyk, J.E.; Cotter, R.J.
Investigation of an albumin-enriched fraction of human serum and
its albuminome. Proteomics Clin. Appl., 2007, 1(1), 73-88.
[http://dx.doi.org/10.1002/prca.200600276] [PMID: 20204147] 
(h)  Lee, G. Biological implications of human serum proteins recognized
by cancerous immunoglobulins. Clin. Res. Immunol., 2018,
1(2), 1-4.
[13] 
Buyuk, G.N.; Oskovi-Kaplan, Z.A.; Durukan, H. Maternal serum haptoglobin levels as a marker of preterm premature rupture of membranes. Z. Geburtshilfe Neonatol.,  2021, 225(1), 47-50.
[http://dx.doi.org/10.1055/a-1167-4512] [PMID: 32464669] 
[14] 
McCarthy, M.E.; Buhimschi, C.S.; Hardy, J.T.; Dulay, A.T.; Laky, C.A.; Bahtyiar, M.O.; Papanna, R.; Zhao, G.; Buhimschi, I.A. Identification of haptoglobin switch-on status in archived placental specimens indicates antenatal exposure to inflammation and potential participation of the fetus in triggering preterm birth. Placenta,  2018, 62, 50-57.
[http://dx.doi.org/10.1016/j.placenta.2017.12.017] [PMID: 29405967] 
[15] 
Khazaei, H.A.; Teymuri, B.; Nakhaei, A.; Mohammadi, M.; Noura, M.; Khazaei, A.; Tofiqh, N.; Rezaei, N. Association of haptoglobin phenotypes with clinical features of preterm labor disease. Acta Med. Iran.,  2013, 51(8), 554-559.
[PMID: 24026993] 
[16] 
Zhu, Y.; Ma, H.; Ma, W. Transthyretin and retinol-binding protein 4 in patients with fetal growth restriction. Clin. Exp. Obstet. Gynecol.,  2019, 46(2), 270-273.
[http://dx.doi.org/10.12891/ceog4636.2019] 
[17] 
Ferguson, K.K.; McElrath, T.F.; Chen, Y.H.; Mukherjee, B.; Meeker, J.D. Longitudinal profiling of inflammatory cytokines and C-reactive protein during uncomplicated and preterm pregnancy. Am. J. Reprod. Immunol.,  2014, 72(3), 326-336.
[http://dx.doi.org/10.1111/aji.12265] [PMID: 24807462] 
[18] 
Challis, J.R.; Lockwood, C.J.; Myatt, L.; Norman, J.E.; Strauss, J.F., III; Petraglia, F. Inflammation and pregnancy. Reprod. Sci.,  2009, 16(2), 206-215.
[http://dx.doi.org/10.1177/1933719108329095] [PMID: 19208789] 
[19] 
Romero, R.; Espinoza, J.; Gonçalves, L.F.; Kusanovic, J.P.; Friel, L.; Hassan, S. The role of inflammation and infection in preterm birth. Seminars Reprod. Med.,  2007, 25(01), 021-039.
[http://dx.doi.org/10.1055/s-2006-956773] 
[20] 
Mendola, P.; Ghassabian, A.; Mills, J.L.; Zhang, C.; Tsai, M.Y.; Liu, A.; Yeung, E.H. Retinol-binding protein 4 and lipids prospectively measured during early to mid-pregnancy in relation to preeclampsia and preterm birth risk. Am. J. Hypertens.,  2017, 30(6), 569-576.
[http://dx.doi.org/10.1093/ajh/hpx020] [PMID: 28338737] 
[21] 
Cetinkaya, S.; Ozaksit, G.; Biberoglu, E.H.; Oskovi, A.; Kirbas, A. The value of acute phase reactants in predicting preterm delivery. J. Matern. Fetal Neonatal Med.,  2017, 30(24), 3004-3008.
[http://dx.doi.org/10.1080/14767058.2016.1271409] [PMID: 27936992] 
[22] 
Raza, N.; Sarwar, I.; Munazza, B.; Ayub, M.; Suleman, M. Assessment of iron deficiency in pregnant women by determining iron status. J. Ayub Med. Coll. Abbottabad,  2011, 23(2), 36-40.
[PMID: 24800338] 

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DOI https://dx.doi.org/10.2174/1570164619666220412122959	Print ISSN 1570-1646
Publisher Name Bentham Science Publisher	Online ISSN 1875-6247

Current Proteomics

Proteomic Profiling of Maternal Serum for Early Risk Analysis of Preterm Birth

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