Table 2. CSF Protein Comparison of Normotensive Pregnant and Nonpregnant Women Analyzed with the Scaffold Methoda,b.
protein name | gene name | t-test | up/down in CO | fold change (CO/NP) | pregnancy hits | total literature hits | ratio pregnancy/total hits | weighted score | reference of first publication |
---|---|---|---|---|---|---|---|---|---|
prolactin | PRL | 2.50 × 10–3 | up | 2.79 | 3624 | 48741 | 0.07 | 269.45 | 10.1210/endo-17-6-689 |
pregnancy zone protein | PZP | <1.00 × 10–4 | up | 1.74 | 197 | 197 | 1.00 | 197.00 | 10.1016/0002-9378(64)90712-4 |
fibronectin | FN1 | 2.20 × 10–3 | down | 0.91 | 643 | 4640 | 0.14 | 89.11 | Kuusela et al., 1978 |
pregnancy-specific β-1-glycoprotein 1 | PSG1 | <1.00 × 10–4 | up | 43.41 | 34 | 62 | 0.55 | 18.65 | 10.1016/0006-291X(89)91105-4 |
sex hormone-binding globulin | SHBG | <1.00 × 10–4 | up | 15.56 | 273 | 5300 | 0.05 | 14.06 | Rager et al., 1972 |
disintegrin and metalloproteinase domain-containing protein 12 | ADAM12 | 2.60 × 10–3 | up | 4.44 | 67 | 357 | 0.19 | 12.57 | 10.1002/pd.762 |
pregnancy-specific β-1-glycoprotein 9 | PSG9 | <1.00 × 10–4 | up | 21.26 | 13 | 14 | 0.93 | 12.07 | 10.1021/bi00496a009 |
pregnancy-specific β-1-glycoprotein 11 | PSG11 | <1.00 × 10–4 | up | 11.88 | 11 | 16 | 0.69 | 7.56 | Kuroki et al., 1991 |
ceruloplasmin | CP | 2.50 × 10–3 | up | 1.16 | 221 | 7444 | 0.03 | 6.56 | 10.3181/00379727-98-24117 |
pregnancy-specific β-1-glycoprotein 4 | PSG4 | <1.00 × 10–4 | up | 17.27 | 9 | 15 | 0.60 | 5.40 | 10.1016/0006-291X(89)91105-4 |
chorionic somatomammotropin hormone 1 | CSH1 | <1.00 × 10–4 | up | 81.57 | 21 | 90 | 0.23 | 4.90 | 10.1373/49.9.1445 |
pregnancy-specific β-1-glycoprotein 3 | PSG3 | <1.00 × 10–4 | up | 16.56 | 11 | 26 | 0.42 | 4.65 | 10.1016/0006-291X(90)91455-2 |
putative pregnancy-specific β-1-glycoprotein 7 | PSG7 | <1.00 × 10–4 | up | 21.41 | 6 | 9 | 0.67 | 4.00 | 10.1016/0006-291X(90)92103-7 |
serum albumin | ALB | <1.00 × 10–4 | down | 0.81 | 540 | 86 597 | 0.01 | 3.37 | 10.1111/j.0954-6820.1921.tb15205.x |
vitamin D binding protein | GC | 9.00 × 10–4 | up | 1.14 | 62 | 1731 | 0.04 | 2.22 | 10.1210/jcem-45-2-225 |
72 kDa type IV collagenase | MMP2 | <1.00 × 10–4 | up | 1.43 | 90 | 4325 | 0.02 | 1.87 | PubMed ID: 11042903 |
insulin-like growth factor-binding protein 3 | IGFBP3 | 8.30 × 10–3 | up | 1.80 | 32 | 1128 | 0.03 | 0.91 | 10.1007/BF02211374 |
pregnancy-specific β-1-glycoprotein 2 | PSG2 | <1.00 × 10–4 | up | 20.53 | 6 | 40 | 0.15 | 0.90 | 10.1016/0006-291X(90)91455-2 |
afamin | AFM | 6.00 × 10–4 | up | 1.34 | 9 | 96 | 0.09 | 0.84 | 10.1002/pd.2040 |
glutathione peroxidase 3 | GPX3 | <1.00 × 10–4 | up | 2.73 | 20 | 488 | 0.04 | 0.82 | Sunde et al., 1998 |
β-2-microglobulin | B2M | 7.00 × 10–4 | up | 1.23 | 55 | 3794 | 0.01 | 0.80 | 10.3109/00365518109090529 |
bone marrow proteoglycan | PRG2 | <1.00 × 10–4 | up | 5.90 | 5 | 33 | 0.15 | 0.76 | 10.1095/biolreprod.110.090209 |
somatostatin | SST | 2.00 × 10–4 | up | 2.30 | 153 | 32 876 | 0.00 | 0.71 | Kumasaka et al., 1978 |
collagen α-1(III) chain | COL3A1 | 4.20 × 10–3 | down | 0.47 | 24 | 890 | 0.03 | 0.65 | 10.1002/(SICI)1096-8628(19990212)82:4<305::AID-AJMG6>3.0.CO;2-C |
histidine-rich glycoprotein | HRG | <1.00 × 10–4 | down | 0.33 | 16 | 415 | 0.04 | 0.62 | 10.3181/00379727-158-40265 |
insulin-like growth factor-binding protein 2 | IGFBP2 | <1.00 × 10–4 | down | 0.69 | 17 | 505 | 0.03 | 0.57 | 10.1210/endo-127-5-2270 |
glutathione S-transferase P | GSTP1 | 2.10 × 10–3 | up | 1.82 | 43 | 3348 | 0.01 | 0.55 | 10.3109/10641959909023074 |
apolipoprotein A-I | APOA1 | 2.00 × 10–4 | up | 1.34 | 30 | 1725 | 0.02 | 0.52 | PubMed ID: 8364102 |
corticosteroid-binding globulin | SERPINA6 | 5.00 × 10–4 | up | 1.56 | 4 | 33 | 0.12 | 0.48 | 10.1002/bdra.20843 |
insulin-like growth factor-binding protein 5 | IGFBP5 | <1.00 × 10–4 | down | 0.36 | 13 | 371 | 0.04 | 0.46 | 10.1095/biolreprod62.5.1415 |
collagen α-1(I) chain | COL1A1 | 4.00 × 10–4 | down | 0.71 | 34 | 2994 | 0.01 | 0.39 | PubMed ID: 2886666 |
collagen α-2(I) chain | COL1A2 | <1.00 × 10–4 | down | 0.71 | 21 | 1270 | 0.02 | 0.35 | PubMed ID: 2886666 |
α-1-antitrypsin | SERPINA1 | <1.00 × 10–4 | up | 1.49 | 11 | 349 | 0.03 | 0.35 | 10.1016/j.ajog.2008.07.006 |
endothelial protein C receptor | PROCR | 1.30 × 10–3 | up | 3.20 | 5 | 82 | 0.06 | 0.30 | 10.1160/TH-09-04-0224 |
growth arrest-specific protein 6 | GAS6 | 1.40 × 10–3 | up | 2.55 | 15 | 750 | 0.02 | 0.30 | 10.1152/ajplung.1998.275.6.L1184 |
transgelin | TAGLN | <1.00 × 10–4 | up | 3.56 | 6 | 143 | 0.04 | 0.25 | 10.1530/REP-09-0208 |
apolipoprotein E | APOE | <1.00 × 10–4 | up | 1.27 | 69 | 19 608 | 0.00 | 0.24 | PubMed ID: 8725150 |
clusterin | CLU | <1.00 × 10–4 | down | 0.80 | 22 | 2311 | 0.01 | 0.21 | 10.1210/endo.136.12.7588296 |
serotransferrin | TF | <1.00 × 10–4 | up | 1.16 | 7 | 253 | 0.03 | 0.19 | 10.1042/bj2570231 |
V-set and immunoglobulin domain-containing protein 4 | VSIG4 | 6.00 × 10–4 | up | 3.66 | 3 | 55 | 0.05 | 0.16 | 10.3321/j.issn:0529-567x.2008.09.004 |
adipocyte enhancer-binding protein 1 | AEBP1 | <1.00 × 10–4 | down | 0.20 | 3 | 64 | 0.05 | 0.14 | 10.1371/journal.pone.0027795 |
lymphatic vessel endothelial hyaluronic acid receptor 1 | LYVE1 | 1.80 × 10–3 | up | 1.56 | 4 | 115 | 0.03 | 0.14 | 10.1095/biolreprod.108.067975 |
extracellular superoxide dismutase [Cu–Zn] | SOD3 | 5.40 × 10–3 | down | 0.85 | 8 | 487 | 0.02 | 0.13 | 10.1016/j.placenta.2010.02.007 |
ectonucleotide pyrophosphatase/phosphodiesterase family member 2 | ENPP2 | 1.40 × 10–3 | down | 0.86 | 4 | 123 | 0.03 | 0.13 | 10.1095/biolreprod.112.099564 |
renin receptor | ATP6AP2 | <1.00 × 10–4 | down | 0.36 | 3 | 73 | 0.04 | 0.12 | 10.1016/j.placenta.2014.09.004 |
14-3-3 protein zeta/delta | YWHAZ | <1.00 × 10–4 | up | 2.19 | 6 | 349 | 0.02 | 0.10 | 10.1016/j.placenta.2004.09.009 |
fibulin-2 | FBLN2 | 4.00 × 10–3 | down | 0.58 | 2 | 39 | 0.05 | 0.10 | 10.1007/s00018-014-1577-4 |
pleiotrophin | PTN | <1.00 × 10–4 | down | 0.17 | 8 | 627 | 0.01 | 0.10 | 10.1210/endo.142.2.8111 |
WAP four-disulfide core domain protein 2 | WFDC2 | 3.70 × 10–3 | up | 2.38 | 2 | 40 | 0.05 | 0.10 | 10.1111/j.1525-142X.2007.00175.x |
inter-α-trypsin inhibitor heavy chain H4 | ITIH4 | 1.60 × 10–3 | up | 1.27 | 3 | 122 | 0.02 | 0.07 | 10.1530/rep.0.1260621 |
interleukin-6 receptor subunit β | IL6ST | 4.30 × 10–3 | up | 1.75 | 3 | 154 | 0.02 | 0.06 | 10.1530/REP-08-0437 |
β-2-glycoprotein 1 | APOH | <1.00 × 10–4 | down | 0.82 | 3 | 166 | 0.02 | 0.05 | 10.1016/j.earlhumdev.2010.06.013 |
polypeptide N-acetylgalactosaminyltransferase 2 | GALNT2 | <1.00 × 10–4 | up | 3.41 | 2 | 77 | 0.03 | 0.05 | 10.1289/ehp.1307892 |
cadherin-18 | CDH18 | 1.10 × 10–3 | up | 1.45 | 1 | 20 | 0.05 | 0.05 | 10.1016/j.tjog.2018.08.023 |
l-lactate dehydrogenase A chain | LDHA | 8.20 × 10–3 | up | 2.36 | 7 | 1008 | 0.01 | 0.05 | 10.1016/j.placenta.2006.11.011 |
insulin-like growth factor-binding protein 7 | IGFBP7 | <1.00 × 10–4 | down | 0.70 | 4 | 364 | 0.01 | 0.04 | 10.1371/journal.pone.0045224 |
peptidyl-prolyl cis-trans isomerase A | PPIA | 2.00 × 10–4 | up | 1.97 | 4 | 424 | 0.01 | 0.04 | 10.1186/1471-2199-10-100 |
heat shock cognate 71 kDa protein | HSPA8 | 3.20 × 10–3 | up | 1.85 | 3 | 246 | 0.01 | 0.04 | 10.1007/s11033-012-2104-z |
profilin-1 | PFN1 | 2.00 × 10–4 | up | 3.03 | 3 | 258 | 0.01 | 0.03 | 10.1371/journal.pone.0031418 |
glutaminyl-peptide cyclotransferase | QPCT | 1.30 × 10–3 | up | 3.53 | 1 | 34 | 0.03 | 0.03 | 10.3390/nu10040417 |
cocaine- and amphetamine-regulated transcript protein | CARTPT | 2.30 × 10–3 | up | 2.23 | 1 | 36 | 0.03 | 0.03 | 10.1038/ijo.2015.38 |
procollagen C-endopeptidase enhancer 1 | PCOLCE | <1.00 × 10–4 | down | 0.26 | 1 | 36 | 0.03 | 0.03 | 10.1089/scd.2013.0334 |
complement factor D | CFD | <1.00 × 10–4 | down | 0.38 | 2 | 156 | 0.01 | 0.03 | 10.1371/journal.pone.0125346 |
peptidyl-glycine α-amidating monooxygenase | PAM | 4.90 × 10–3 | up | 1.24 | 1 | 45 | 0.02 | 0.02 | 10.1016/j.theriogenology.2016.10.007 |
apolipoprotein A-II | APOA2 | 1.80 × 10–3 | up | 1.46 | 2 | 188 | 0.01 | 0.02 | 10.1262/jrd.18002 |
matrix gla protein | MGP | 3.60 × 10–3 | down | 0.42 | 4 | 863 | 0.00 | 0.02 | 10.1111/j.1834-7819.1994.tb01379.x |
α-enolase | ENO1 | <1.00 × 10–4 | up | 2.68 | 4 | 922 | 0.00 | 0.02 | 10.1076/apab.110.1.94.897 |
cadherin EGF LAG seven-pass G-type receptor 2 | CELSR2 | <1.00 × 10–4 | down | 0.30 | 1 | 87 | 0.01 | 0.01 | 10.3389/fgene.2019.00540 |
spondin-1 | SPON1 | <1.00 × 10–4 | down | 0.23 | 1 | 90 | 0.01 | 0.01 | 10.1071/RD18114 |
ATP-binding cassette subfamily A member 2 | ABCA2 | <1.00 × 10–4 | up | 5.21 | 1 | 92 | 0.01 | 0.01 | 10.1074/jbc.M611056200 |
lysosome-associated membrane glycoprotein 2 | LAMP2 | 3.00 × 10–4 | up | 1.79 | 2 | 471 | 0.00 | 0.01 | 10.1016/j.amjcard.2011.09.024 |
thrombospondin-2 | THBS2 | 2.80 × 10–3 | down | 0.26 | 1 | 161 | 0.01 | 0.01 | 10.1262/jrd.2016-056 |
basal cell adhesion molecule | BCAM | 4.60 × 10–3 | up | 2.14 | 1 | 176 | 0.01 | 0.01 | 10.3233/CH-2011-1525 |
A reference to the literature was included to define the association of the particular protein in pregnancy.
A total number of 135 proteins was found with a p-value of less than p = 0.0086 (Benjamini–Hochberg) when comparing the normotensive pregnant women with nonpregnant women. Seventy-three (out of 135) proteins were described in the literature as being associated with pregnancy listed above. Each protein was ranked to their weighted score in the Scopus citation database search (November 2019) related to pregnancy. In the last column, the first published paper is listed. As an example, prolactin has the highest score for a protein described to associate with pregnancy. Proteins (n = 62) with zero counts (no association with pregnancy) for the weighted score are shown in Table S3, Supporting Information. CO = normotensive pregnant women; NP = nonpregnant women.