Spatial Proteomic Analysis of Isogenic Metastatic Colorectal Cancer Cells Reveals Key Dysregulated Proteins Associated with Lymph Node, Liver, and Lung Metastasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. CRC Cell Lines
2.2. Protein Extracts and Quantification
2.3. TMT 11-Plex Labeling
2.4. LC–MS/MS Analysis
2.5. MS Data Analysis
2.6. Tissue and Plasma Samples
2.7. Western Blot
2.8. Immunofluorescence
2.9. In Silico Analysis
2.10. Immunohistochemistry, Tissue Microarrays and ELISA
2.11. Statistical Analysis
3. Results
3.1. Subcellular Fractionation and Analysis for Differential Protein Expression and Localization in Lymph Nodes, Liver and Lung Metastatic Tropism of Colorectal Cancer Cells
3.2. Mapping Spatial Protein Alterations in CRC Metastatic Cells
3.3. Protein clusters, Pathways and Network Analysis of Differentially Expressed Proteins in CRC Metastatic Cells
3.4. Validation of Dysregulation of Proteins in Abundance and/or Localization
3.5. Relevance of Dysregulated Proteins in Colorectal Cancer
3.6. GLG1 Analysis as Blood-Based Candidate Biomarkers for Colorectal Cancer Diagnosis
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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Application | Samples (n) | Age Average ± SD (Years) | Age Range (Years) | Gender (n) | Stage | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Male | Female | Premalignant Individuals | I | II | III | IV | ||||||
Tissue samples | WB analysis | CRC patients | 14 | 72.1 ± 12.3 | 47–88 | 5 | 9 | - | 2 | 4 | 4 | 4 |
IHC and TMA analysis | CRC patients | 95 | 73.0 ± 9.6 | 94–51 | 57 | 38 | - | 3 | 30 | 61 | 1 | |
Plasma samples | ELISA | CRC patients | 48 | 73.2 ± 10.3 | 49–88 | 21 | 27 | 10 | 10 | 10 | 11 | 7 |
Healthy individuals | 32 | 57.9 ± 10.4 | 24–74 | 16 | 16 | - |
Protein | Accession Number | Association | Compartment | Fold Change * | Up- or Downregulated |
---|---|---|---|---|---|
GAS6 | Q14393 | Metastatic cells | Secretome | 37.24 | Up |
DCD | P81605 | Metastatic cells | Secretome | 35.46 | Up |
c-MET | P08581 | Metastatic cells | Secretome | 23.31 | Up |
LMAN1 | P49257 | Metastatic cells | Secretome | 19.17 | Up |
CEMIP | Q8WUJ3 | Metastatic cells | Secretome | 12.39 | Up |
HMGN5 | P82970 | Metastatic cells | PEB | 11.34 | Up |
MUC5AC | P98088 | Metastatic cells | MEB | 9.85 | Up |
TNFRSF10A | O00220 | Metastatic cells | CEB | 9.37 | Up |
VIL1 | P09327 | Metastatic cells | NEB | 7.71 | Up |
GLG1 | Q92896 | Metastatic cells | Secretome | 7.54 | Up |
LCP1 | P13796 | Metastatic cells | CEB | 6.30 | Up |
AGR3 | Q8TD06 | Metastatic cells | Secretome | 5.51 | Up |
PLS3 | P13797 | Metastatic cells | Secretome | 5.33 | Up |
CDKN2AIP | Q9NXV6 | Metastatic cells | CEB | 5.04 | Up |
SNX9 | Q9Y5X1 | Liver and Lung metastasis | Secretome | 4.97 | Up |
PHYHIPL | Q96FC7 | Metastatic cells | MEB | 4.07 | Up |
ARHGAP18 | Q8N392 | Metastatic cells | NEB | 4.01 | Up |
S100A16 | Q96FQ6 | Metastatic cells | NEB | 3.98 | Up |
FBP1 | P09467 | Metastatic cells | CEB | 3.96 | Up |
S100P | P25815 | Metastatic cells | Secretome | 3.30 | Up |
PTRF | Q6NZI2 | Metastatic cells | NBP | 3.02 | Up |
CLDN3 | O15551 | Liver and Liver and Lung metastasis | PEB | 2.57 | Up |
AHR | P35869 | Liver and Lung metastasis | NBP | 2.52 | Up |
SCRIB | Q14160 | Liver metastasis | MEB | 2.13 | Up |
MAP2K3 | P46734 | Metastatic cells | NBP | 2.10 | Up |
KIF13B | Q9NQT8 | Metastatic cells | PEB | 2.06 | Up |
BAIAP2 | Q9UQB8 | Lymph nodes metastasis | MEB | 2.04 | Up |
LGALS1 | P09382 | Metastatic cells | CEB | 0.20 | Down |
PHLDB1 | Q86UU1 | Metastatic cells | MEB | 0.19 | Down |
SLC2A1 | P11166 | Metastatic cells | MEB | 0.18 | Down |
FYCO1 | Q9BQS8 | Metastatic cells | MEB | 0.16 | Down |
L1CAM | P32004 | Metastatic cells | MEB | 0.16 | Down |
ASS1 | P00966 | Metastatic cells | Secretome | 0.15 | Down |
ICAM1 | P05362 | Metastatic cells | MEB | 0.15 | Down |
MCAM | P43121 | Metastatic cells | MEB | 0.13 | Down |
TGM2 | P21980 | Metastatic cells | Secretome | 0.05 | Down |
CRABP2 | P29373 | Metastatic cells | Secretome | 0.02 | Down |
RBP1 | P09455 | Metastatic cells | Secretome | 0.02 | Down |
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Solís-Fernández, G.; Montero-Calle, A.; Martínez-Useros, J.; López-Janeiro, Á.; de los Ríos, V.; Sanz, R.; Dziakova, J.; Milagrosa, E.; Fernández-Aceñero, M.J.; Peláez-García, A.; et al. Spatial Proteomic Analysis of Isogenic Metastatic Colorectal Cancer Cells Reveals Key Dysregulated Proteins Associated with Lymph Node, Liver, and Lung Metastasis. Cells 2022, 11, 447. https://doi.org/10.3390/cells11030447
Solís-Fernández G, Montero-Calle A, Martínez-Useros J, López-Janeiro Á, de los Ríos V, Sanz R, Dziakova J, Milagrosa E, Fernández-Aceñero MJ, Peláez-García A, et al. Spatial Proteomic Analysis of Isogenic Metastatic Colorectal Cancer Cells Reveals Key Dysregulated Proteins Associated with Lymph Node, Liver, and Lung Metastasis. Cells. 2022; 11(3):447. https://doi.org/10.3390/cells11030447
Chicago/Turabian StyleSolís-Fernández, Guillermo, Ana Montero-Calle, Javier Martínez-Useros, Álvaro López-Janeiro, Vivian de los Ríos, Rodrigo Sanz, Jana Dziakova, Elena Milagrosa, María Jesús Fernández-Aceñero, Alberto Peláez-García, and et al. 2022. "Spatial Proteomic Analysis of Isogenic Metastatic Colorectal Cancer Cells Reveals Key Dysregulated Proteins Associated with Lymph Node, Liver, and Lung Metastasis" Cells 11, no. 3: 447. https://doi.org/10.3390/cells11030447