Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases
Abstract
:1. Introduction
2. Results
2.1. Clinical Data
2.2. Proteome Description
2.3. Classification of the FOLFOX-Treated and Control Group on the Basis of Protein Expression
2.4. Proteome Differences between FOLFOX-Treated and Control Group
2.5. Protein Ontology and Pathway Analysis
3. Discussion
4. Materials and Methods
4.1. Patients and Liver Tissue Samples
4.2. Preparation of Tissue Lysates
4.3. Sample Processing
4.4. Removal of Substances Affecting Liquid Chromatography–Tandem Mass Spectrometry (LC–MS/MS)
4.5. LC–MS/MS and Raw Data Analysis
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
CRLM | Colo-Rectal cancer Liver Metastases |
FOLFOX | Fluorouracil Leucovorin Oxaliplatin treatment |
SI | Sinusoidal Injury |
PCA | Principal Component Analysis |
RFE-SVM | Recursive Feature Elimination-Support Vector Machine |
FDR | False Discovery Ratio |
MCM | minichromosome maintenance complex |
LC-MS/MS | Liquid chromatography-tandem mass spectrometry |
References
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Gene Names | Protein Names | Welch t-Test p-Value | Fold Change | Coefficient of Variation | Peptides | Unique Peptides |
---|---|---|---|---|---|---|
MAP1B | Microtubule-associated protein 1B;MAP1 light chain LC1 | 0.007 | 10.21 | 1.43 | 24 | 23 |
HLA-DQA1 | Major histocompatibility complex, class II, DQ alpha 1 | 0.002 | 6.23 | 1.12 | 4 | 2 |
C19orf52 | Uncharacterized protein C19orf52 | 0.012 | 4.90 | 1.92 | 3 | 3 |
IGHD | Ig delta chain C region | 0.022 | 3.88 | 1.82 | 7 | 7 |
MCM2 | DNA replication licensing factor MCM2 | 0.002 | 3.40 | 0.80 | 12 | 12 |
MLIP | Muscular LMNA-interacting protein | 0.001 | 3.11 | 0.74 | 4 | 4 |
STMN2 | Stathmin-2 | 0.021 | 3.02 | 0.93 | 1 | 1 |
Q7Z7K6 | Centromere protein V | 0.013 | 2.84 | 1.37 | 8 | 3 |
MCM4 | DNA replication licensing factor MCM4 | 0.007 | 2.71 | 0.82 | 7 | 7 |
EMG1 | Ribosomal RNA small subunit methyltransferase NEP1 | 0.017 | 2.63 | 1.17 | 4 | 4 |
NUDT12 | Peroxisomal NADH pyrophosphatase NUDT12 | 0.009 | 2.38 | 0.73 | 8 | 8 |
DHFR; DHFRL1 | Dihydrofolate reductase;Dihydrofolate reductase, mitochondrial | 0.014 | 2.31 | 0.62 | 2 | 2 |
OSBPL6 | Oxysterol-binding protein-related protein 6 | 0.010 | 2.25 | 0.84 | 3 | 3 |
MCM7 | DNA replication licensing factor MCM7 | 0.012 | 2.20 | 0.71 | 11 | 11 |
ANGPTL3 | Angiopoietin-related protein 3 | 0.009 | 2.14 | 0.62 | 5 | 5 |
TMEM2 | Transmembrane protein 2 | 0.002 | 2.02 | 0.51 | 4 | 4 |
DDX20 | Probable ATP-dependent RNA helicase DDX20 | 0.006 | 1.94 | 0.54 | 4 | 4 |
ISG15 | Ubiquitin-like protein ISG15 | 0.010 | 1.82 | 0.67 | 5 | 5 |
CCDC25 | Coiled-coil domain-containing protein 25 | 0.004 | 1.79 | 0.59 | 9 | 9 |
NBEAL1 | Neurobeachin-like protein 1 | 0.009 | 1.63 | 0.52 | 10 | 10 |
BCO2 | Beta,beta-carotene 9,10-oxygenase | 0.009 | 1.57 | 0.43 | 22 | 22 |
HAL | Histidine ammonia-lyase | 0.013 | −1.65 | 0.46 | 25 | 25 |
ASAH1 | Acid ceramidase;Acid ceramidase subunit alpha;Acid ceramidase subunit beta | 0.000 | −1.66 | 0.38 | 15 | 15 |
CYP2S1 | Cytochrome P450 2S1 | 0.008 | −1.72 | 0.45 | 2 | 2 |
GPX1 | Glutathione peroxidase 1 | 0.011 | −1.76 | 0.55 | 13 | 13 |
CLEC16A | Protein CLEC16A | 0.013 | −1.76 | 0.60 | 1 | 1 |
ACTR1B | Beta-centractin | 0.015 | −1.83 | 0.51 | 9 | 4 |
CHMP1A | Charged multivesicular body protein 1a | 0.009 | −1.87 | 0.56 | 1 | 1 |
CTBS | Di-N-acetylchitobiase | 0.012 | −1.98 | 0.71 | 5 | 5 |
FOLH1; FOLH1B | Glutamate carboxypeptidase 2;Putative N-acetylated-alpha-linked acidic dipeptidase | 0.014 | −2.01 | 0.74 | 8 | 8 |
KHNYN | Protein KHNYN | 0.002 | −2.02 | 0.59 | 2 | 2 |
FRG1 | Protein FRG1 | 0.017 | −2.17 | 0.92 | 3 | 3 |
SRP72 | Signal recognition particle 72 kDa protein | 0.001 | −2.22 | 0.68 | 19 | 19 |
PLSCR3 | Phospholipid scramblase 3 | 0.012 | −2.23 | 0.56 | 2 | 2 |
ERF | ETS domain-containing transcription factor ERF | 0.013 | −2.25 | 0.66 | 3 | 3 |
FNBP1 | Formin-binding protein 1 | 0.014 | −2.28 | 0.75 | 5 | 5 |
SEPP1 | Selenoprotein P | 0.018 | −2.34 | 0.69 | 2 | 2 |
RHPN2 | Rhophilin-2 | 0.009 | −2.40 | 0.89 | 4 | 4 |
ELOVL1 | Elongation of very long chain fatty acids protein 1 | 0.019 | −2.46 | 1.61 | 2 | 2 |
MRPS7 | 28S ribosomal protein S7, mitochondrial | 0.015 | −2.48 | 0.76 | 9 | 9 |
RIN1 | Ras and Rab interactor 1 | 0.012 | −2.82 | 0.55 | 2 | 2 |
ITIH5 | Inter-alpha-trypsin inhibitor heavy chain H5 | 0.008 | −2.95 | 1.23 | 3 | 3 |
CAMK2G; CAMK2A; CAMK2B | Calcium/calmodulin-dependent protein kinase type II subunit gamma;Calcium/calmodulin-dependent protein kinase type II subunit alpha | 0.011 | −2.96 | 0.88 | 8 | 2 |
NT5DC2 | 5-nucleotidase domain-containing protein 2 | 0.006 | −3.04 | 0.92 | 4 | 4 |
FAN1 | Fanconi-associated nuclease 1 | 0.011 | −3.09 | 1.02 | 3 | 3 |
OXNAD1 | Oxidoreductase NAD-binding domain-containing protein 1 | 0.003 | −3.20 | 1.04 | 5 | 5 |
ALOX5AP | Arachidonate 5-lipoxygenase-activating protein | 0.014 | −3.34 | 1.25 | 2 | 2 |
MACF1 | Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 | 0.016 | −3.52 | 1.57 | 83 | 0 |
CPA3 | Mast cell carboxypeptidase A | 0.008 | −3.67 | 1.72 | 4 | 4 |
KRT80 | Keratin, type II cytoskeletal 80 | 0.005 | −3.67 | 0.64 | 5 | 4 |
MYBPC2 | Myosin-binding protein C, fast-type | 0.004 | −4.29 | 0.96 | 4 | 3 |
ERAP2 | Endoplasmic reticulum aminopeptidase 2 | 0.022 | −4.59 | 0.99 | 20 | 20 |
YOD1 | Ubiquitin thioesterase OTU1 | 0.017 | −4.95 | 1.56 | 3 | 3 |
TLCD1 | TLC domain-containing protein 1 | 0.022 | −5.37 | 2.22 | 2 | 2 |
UBE3B | Ubiquitin-protein ligase E3B | 0.024 | −6.17 | 0.96 | 7 | 7 |
Category | Term | Welch t-Test Significant Proteins (n = 55) | Classifying Model Selected Proteins (n = 184) | ||||
---|---|---|---|---|---|---|---|
p-Value | p-Value FDR | Intersection Genes | p-Value | p-Value FDR | Intersection Genes | ||
Biological Process | DNA unwinding involved in replication | <0.001 | 0.013 | MCM2; MCM4; MCM7 | <0.001 | 0.007 | MCM2; MCM4; MCM6; MCM7 |
innate immune response | <0.001 | 0.029 | BCL2; C4B; CAMK2B; CD4; ENSG00000228284; HCK; HLA-DR4; IGKV4-1; IGLV7-43; ISG15; LGALS3; MAPKAPK3; MBL2; MX1; NCAM1; RPS6KA1; VNN1 | ||||
Cellular Component | MCM complex | <0.001 | <0.001 | MCM4; MCM5; MCM6; MCM7 | |||
Pathway | DNA replication | <0.001 | 0.013 | MCM2; MCM4; MCM7 | <0.001 | 0.021 | MCM2; MCM4; MCM5; MCM6; MCM7 |
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Urdzik, J.; Vildhede, A.; Wiśniewski, J.R.; Duraj, F.; Haglund, U.; Artursson, P.; Norén, A. Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases. Proteomes 2016, 4, 30. https://doi.org/10.3390/proteomes4040030
Urdzik J, Vildhede A, Wiśniewski JR, Duraj F, Haglund U, Artursson P, Norén A. Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases. Proteomes. 2016; 4(4):30. https://doi.org/10.3390/proteomes4040030
Chicago/Turabian StyleUrdzik, Jozef, Anna Vildhede, Jacek R. Wiśniewski, Frans Duraj, Ulf Haglund, Per Artursson, and Agneta Norén. 2016. "Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases" Proteomes 4, no. 4: 30. https://doi.org/10.3390/proteomes4040030