Unveiling Distinct Proteomic Signatures in Complicated Crohn’s Disease That Could Predict the Disease Course
Abstract
:1. Introduction
2. Results
2.1. Baseline Characteristics of the Study Participants
2.2. Serum Proteome Characterization
2.2.1. Deciphering Serum Proteome Group Patterns
2.2.2. Serum Proteome Alterations in Crohn’s Disease
2.2.3. Serum Proteome Alterations in the Aggressive Crohn’s Disease Phenotype
2.3. Biomarker Signature Scouting toward Disease Course Prediction
2.4. Proteome Correlation with Clinical Biomarkers
3. Discussion
4. Materials and Methods
4.1. Study Participants and Sampling
4.2. Sample Preparation for Proteomics Analysis
4.2.1. Depletion of Six Highly Abundant Serum Proteins
4.2.2. Proteolytic Digestion by Trypsin
4.3. Proteome Profiling with Mass Spectrometry
4.3.1. Protein Identification and Quantification with Nano-LC-HDMSE
4.3.2. Database Search
4.4. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristic | Crohn’s Disease B1 (n = 15) | Crohn’s Disease B2B3 (n = 15) | p-Value * |
---|---|---|---|
Age, years | 39 [31 to 45.5] {24 to 57} | 31 [23.5 to 35] {18 to 44} | 0.018 |
Male, no/n | 7/15 | 8/15 | 0.715 |
Smoking | 0.959 | ||
Current | 3/15 | 3/15 | |
Former | 4/15 | 5/15 | |
Never | 5/15 | 5/15 | |
Unknown | 3/15 | 2/15 | |
Baseline CRP (mg/dL) | 0.4 [0.4 to 2.8] {0.31 to 4.48} | 1 [0.4 to 5] {0.29 to 13.47} | 0.237 |
Baseline ALB (g/dL) | 4 [3.9 to 4.1] {0.85 to 5.1} | 3.7 [3.2 to 4.1] {2.5 to 5.6} | 0.351 |
Baseline FCal (µg/g) | 200 [155 to 380] {20 to 860} | 600 [300 to 910] {15 to 2300} | 0.059 |
Montreal age (A) | 0.636 | ||
A1 (<17 years) | 1/15 | 3/15 | |
A2 (17–40 years) | 12/15 | 10/15 | |
A3 (>40 years) | 2/15 | 2/15 | |
Montreal location (L) | 0.532 | ||
L1 (Terminal ileum) | 6/15 | 3/15 | |
L2 (Colon) | 4/15 | 4/15 | |
L3 (Ileo-colon) | 5/15 | 7/15 | |
L4 (Upper GI) | 0/15 | 1/15 | |
Montreal behavior (B) | not applicable | ||
B1 (non-stricturing, non-penetrating) | 15/15 | 0/15 | |
B2 (stricturing) | 0/15 | 8/15 | |
B3 (penetrating) | 0/15 | 3/15 | |
B2 + B3 | 0/15 | 4/15 | |
Perianal disease | 3/15 | 4/15 | 0.805 |
Baseline HBI | 6 [4 to 8] | 9 [8 to 9.5] | 0.014 |
Baseline SES-CD score | 6 [4 to 8] | 13 [6 to 18] | 0.019 |
Baseline imaging ** | |||
Inflammation | 10/15 | 14/15 | 0.44 |
Stenosis | 0/15 | 10/15 | <0.001 |
Fistulae | 0/15 | 4/15 | 0.079 |
Abscess (intraabdominal) | 0/15 | 2/15 | 0.303 |
Baseline medication | |||
5-ASA | 10/15 | 6/15 | 0.136 |
Azathioprine | 9/15 | 11/15 | 0.35 |
Budesonide/Prednisolone | 4/15 | 2/15 | 0.326 |
Anti-TNFα# | 8/15 | 14/15 | 0.018 |
History of IBD-related surgery | 15 | 15 | 0.086 |
Characteristic at 1-Year Follow Up | Crohn’s Disease B1 (n = 15) | Crohn’s Disease B2B3 (n = 15) | p-Value * |
---|---|---|---|
HBI | 2 [2 to 3] {0 to 6} | 3 [3 to 4.5] {0 to 11} | 0.1533 |
CRP (mg/dL) | 0.44 [0.35 to 0.5] {0.28 to 2.56} | 0.43 [0.335 to 0.975] {0.28 to 18.54} | 0.9449 |
ALB (g/dL) | 4.1 [3.9 to 4.2] {3.6 to 5.2} | 4.2 [3.85 to 4.45] {3.6 to 5.3} | 0.7471 |
FCal (µg/g) | 50 [50 to 65] {5 to 240} | 70 [50 to 141] {18 to 700} | 0.2136 |
SES-CD score | 2 [1.5 to 4.25]{0 to 5} | 5 [3 to 6]{0 to 8} | 0.1779 |
Surgery | 1/13 | 5/15 | 0.2338 |
Treatment escalation/Biologic change | 3/13 | 2/15 | 0.7345 |
No. | Protein Name | Gene | ANOVA, x = Significant | Fold Change | |||||
---|---|---|---|---|---|---|---|---|---|
B1 vs. HC | B2B3 vs. HC | B2B3 vs. B1 | B1 vs. HC | B2B3 vs. HC | B2B3 vs. B1 | B1 vs. B2B3 | |||
1 | Albumin | ALB | x | x | 0.68 | 0.19 | 0.28 | 3.54 | |
2 | Alpha-1-antichymotrypsin | SERPINA3 | x | x | 1.35 | 1.77 | 1.31 | 0.76 | |
3 | Charged multivesicular body protein 3 | CHMP3 | x | x | 0.63 | 0.24 | 0.38 | 2.61 | |
4 | Complement component C9 | C9 | x | 1.40 | 1.59 | 1.14 | 0.88 | ||
5 | Complement factor I | CFI | x | 1.13 | 1.34 | 1.18 | 0.85 | ||
6 | DNA polymerase epsilon catalytic subunit A | POLE | x | x | 1.28 | 1.52 | 1.19 | 0.84 | |
7 | Dynein axonemal heavy chain 7 | DNAH7 | x | x | 0.70 | 0.26 | 0.37 | 2.69 | |
8 | Epididymal secretory glutathione peroxidase | GPX5 | x | x | 0.58 | 0.11 | 0.20 | 5.07 | |
9 | GDH/6PGL endoplasmic bifunctional protein | H6PD | x | x | 1.61 | 2.33 | 1.45 | 0.69 | |
10 | Haptoglobin | HP | x | x | 7.95 | 7.72 | 0.97 | 1.03 | |
11 | Haptoglobin-related protein | HPR | x | x | 2.20 | 2.92 | 1.33 | 0.75 | |
12 | High mobility group nucleosome binding domain 5 | HMGN5 | x | x | 0.89 | 1.36 | 1.53 | 0.65 | |
13 | Immunoglobulin kappa constant | IGKC | x | x | 1.26 | 1.70 | 1.35 | 0.74 | |
14 | Leucine-rich alpha-2-glycoprotein | LRG1 | x | x | 1.46 | 2.33 | 1.60 | 0.63 | |
15 | Lumican | LUM | x | x | 0.71 | 0.39 | 0.55 | 1.83 | |
16 | Lysine-specific demethylase 3A | KDM3A | x | x | 0.69 | 0.31 | 0.45 | 2.24 | |
17 | Microtubule-associated protein 1A | MAP1A | x | x | 1.43 | 1.48 | 1.04 | 0.97 | |
18 | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic γ | PIK3CG | x | x | 0.64 | 0.18 | 0.28 | 3.58 | |
19 | Phosphatidylinositol 5-phosphate 4-kinase type-2 α | PIP4K2A | x | 1.13 | 1.47 | 1.30 | 0.77 | ||
20 | Plasma serine protease inhibitor | SERPINA5 | x | x | 0.68 | 0.33 | 0.48 | 2.07 | |
21 | Plexin-A2 | PLXNA2 | x | x | 0.66 | 0.22 | 0.33 | 2.99 | |
22 | PTB domain-containing engulfment adapter protein 1 | GULP1 | x | x | 1.21 | 1.54 | 1.27 | 0.79 | |
23 | Putative inactive neutral ceramidase B | ASAH2B | x | 1.36 | 1.86 | 1.37 | 0.73 | ||
24 | Serine/threonine-protein kinase OSR1 | OXSR1 | x | 1.66 | 1.56 | 0.94 | 1.07 | ||
25 | Serum amyloid A-1 protein | SAA1 | x | x | 2.56 | 4.15 | 1.62 | 0.62 | |
26 | Tetratricopeptide repeat protein 9A | TTC9 | x | x | 0.62 | 0.15 | 0.25 | 4.05 | |
27 | Transgelin-2 | TAGLN2 | x | x | 1.39 | 1.46 | 1.05 | 0.95 | |
28 | Translationally controlled tumor protein | TPT1 | x | x | 1.47 | 2.05 | 1.40 | 0.72 | |
29 | WD repeat-containing protein 31 | WDR31 | x | x | 4.69 | 12.87 | 2.74 | 0.36 |
No. | Protein Name | Gene | Diagnosis | HBI | CRP | ALB | FCal | HBI at 1 Year |
---|---|---|---|---|---|---|---|---|
1 | WD repeat-containing protein 31 | WDR31 | 0.42 | 0.50 | 0.65 | −0.32 | 0.39 | 0.03 |
2 | Leucine-rich alpha-2-glycoprotein | LRG1 | 0.45 | 0.40 | 0.48 | −0.15 | 0.37 | 0.04 |
3 | Serum amyloid A-1 protein | SAA1 | 0.50 | 0.40 | 0.61 | −0.28 | 0.37 | 0.06 |
4 | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform | PIK3CG | −0.54 | −0.51 | −0.20 | −0.03 | −0.23 | −0.14 |
5 | Albumin | ALB | −0.57 | −0.53 | −0.30 | 0.13 | −0.25 | −0.14 |
6 | Plexin-A2 | PLXNA2 | −0.53 | −0.57 | −0.29 | 0.14 | −0.30 | −0.15 |
7 | Charged multivesicular body protein 3 | CHMP3 | −0.48 | −0.44 | −0.37 | −0.01 | −0.19 | −0.09 |
8 | Lysine-specific demethylase 3A | KDM3A | −0.53 | −0.45 | −0.22 | 0.14 | −0.17 | −0.14 |
9 | Plasma serine protease inhibitor | SERPINA5 | −0.42 | −0.49 | −0.42 | 0.16 | −0.23 | −0.02 |
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Lucaciu, L.A.; Seicean, R.; Uifălean, A.; Iacobescu, M.; Iuga, C.A.; Seicean, A. Unveiling Distinct Proteomic Signatures in Complicated Crohn’s Disease That Could Predict the Disease Course. Int. J. Mol. Sci. 2023, 24, 16966. https://doi.org/10.3390/ijms242316966
Lucaciu LA, Seicean R, Uifălean A, Iacobescu M, Iuga CA, Seicean A. Unveiling Distinct Proteomic Signatures in Complicated Crohn’s Disease That Could Predict the Disease Course. International Journal of Molecular Sciences. 2023; 24(23):16966. https://doi.org/10.3390/ijms242316966
Chicago/Turabian StyleLucaciu, Laura A., Radu Seicean, Alina Uifălean, Maria Iacobescu, Cristina A. Iuga, and Andrada Seicean. 2023. "Unveiling Distinct Proteomic Signatures in Complicated Crohn’s Disease That Could Predict the Disease Course" International Journal of Molecular Sciences 24, no. 23: 16966. https://doi.org/10.3390/ijms242316966