Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tissue Samples
2.2. TMA Construction
2.3. Mass Spectrometry Imaging
2.4. Histopathological Staining and Annotation
2.5. MALDI-MSI Data Processing
2.6. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)
2.7. Statistical Analysis
2.7.1. Discriminative m/z Signals
2.7.2. Functional Enrichment Analysis
2.7.3. Independent Comparative Validation
3. Results
3.1. Patients, Tumor Samples and Tissue Annotation
3.2. Protein Identification and Discriminative m/z Signals between Low and High Grade Intratumor Regions
3.3. Functional Enrichment Analysis of Differentially Expressed Peptides between Well and Poorly Differentiated Tumor Populations
3.4. Tissue Distribution of FNDC1 and A1BG Peptides
3.5. Prognostic Value of FNDC1, A1BG, CANX, HSPA5 and PDIA3 in Human Breast Cancer Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Biological Process | Fold Enrichment | IDs | FDR |
---|---|---|---|
Protein folding in endoplasmic reticulum | >100 | CANX, HSPA5, PDIA3 | 2.7 × 10−2 |
Extracellular matrix structural constituent conferring tensile strength | 52.16 | COL1A1, COL1A2, COL6A3, COL12A1 | 1.73 × 10−3 |
Extracellular matrix structural constituent | 18.98 | COL1A1, COL1A2, COL6A3, COL12A1, VCAN, EMILIN2 | 1.3 × 10−3 |
Structural molecule activity | 6.81 | COL1A1, COL1A2, COL6A3, COL12A1, VCAN, EMILIN2, LMNA, EPB41L2, CTNNA1 | 4.95 × 10−3 |
Cadherin binding Cell adhesion molecule binding | 17.75 11.01 | LIMA1, EEF1D, CALD1, TNKS1BP1, HSPA5, FLNA, TAGLN2, SERBP1, DDX3X, CTNNA1, BAG3 | 1.07 × 10−7 9.50 × 10−6 |
Pathway Name | Fold Enrichment | IDs | FDR |
---|---|---|---|
GP1b-IX-V activation signaling | >100 | COL1A1, COL1A2, FLNA | 2.47 × 10−3 |
Platelet activation signaling and aggregation | 12.39 | COL1A1, COL1A2, FLNA, A1BG, HSPA5, TAGLN2 | 4.13 × 10−3 |
Antigen presentation: folding, assembly and peptide loading of class I MHC | 61.69 | CANX, HSPA5, PDIA3 | 4.85 × 10−3 |
Collagen chain trimerization | 48.60 | COL1A1, COL1A2, COL6A3, COL12A1 | 4.34 × 10−3 |
Collagen biosynthesis and modifying enzymes | 31.92 | COL1A1, COL1A2, COL6A3, COL12A1 | 3.51 × 10−3 |
Collagen formation | 24.03 | COL1A1, COL1A2, COL6A3, COL12A1 | 5.58 × 10−3 |
Assembly of collagen fibrils and other multimeric structures | 35.64 | COL1A1, COL1A2, COL6A3, COL12A1 | 4.63 × 10−3 |
Collagen degradation | 33.42 | COL1A1, COL1A2, COL6A3, COL12A1 | 4.43 × 10−3 |
Degradation of the extracellular matrix | 15.28 | COL1A1, COL1A2, COL6A3, COL12A1 | 2.41 × 10−2 |
ECM proteoglycans | 28.14 | COL1A1, COL1A2, COL6A3, VCAN | 4.83 × 10−3 |
Platelet degranulation | 16.84 | A1BG, HSPA5, FLNA, TAGLN2 | 1.95 × 10−2 |
Response to elevated platelet cutosolic Ca2+ | 16.20 | A1BG, HSPA5, FLNA, TAGLN2 | 2.08 × 10−2 |
Signaling by receptor tyrosine kinases | 8.19 | COL1A1, COL1A2, COL6A3, STMN1, HNRNPM, CSN2, CTNNA1 | 5.38 × 10−3 |
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Cordeiro, Y.G.; Mulder, L.M.; van Zeijl, R.J.M.; Paskoski, L.B.; van Veelen, P.; de Ru, A.; Strefezzi, R.F.; Heijs, B.; Fukumasu, H. Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer. Cancers 2021, 13, 5901. https://doi.org/10.3390/cancers13235901
Cordeiro YG, Mulder LM, van Zeijl RJM, Paskoski LB, van Veelen P, de Ru A, Strefezzi RF, Heijs B, Fukumasu H. Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer. Cancers. 2021; 13(23):5901. https://doi.org/10.3390/cancers13235901
Chicago/Turabian StyleCordeiro, Yonara G., Leandra M. Mulder, René J. M. van Zeijl, Lindsay B. Paskoski, Peter van Veelen, Arnoud de Ru, Ricardo F. Strefezzi, Bram Heijs, and Heidge Fukumasu. 2021. "Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer" Cancers 13, no. 23: 5901. https://doi.org/10.3390/cancers13235901