Understanding Ovarian Cancer: iTRAQ-Based Proteomics for Biomarker Discovery
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Samples
4.2. Protein Digestion
4.3. iTRAQ Labeling
4.4. nanoLC-MALDI-TOF/TOF MS/MS Analysis
4.5. Database Search and Data Processing
4.6. Quantification of Individual Proteins by ELISA
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
OC | ovarian cancer |
FIGO | International Federation of Gynaecology and Obstetrics |
CA125 | cancer antigen 125 |
HE4 | human epididymis protein 4 |
RMI | Risk of Malignancy Index |
SILAC | stable isotope labelling by amino acids in cell culture |
ICAT | Isotope-coded affinity tag |
ITRAQ | isobaric Tags for Relative and Absolute Quantification |
MALDI-TOF | matrix-assisted laser desorption/ionization time-of-flight |
MS | mass spectrometry |
BOT | benign ovarian tumors |
HC | Healthy controls |
ELISA | enzyme-linked immunosorbent assay |
SC | sequences coverage |
MW | molecular weight |
CRP | C-reactive protein |
FGA | Fibrinogen alpha chain |
APOC2 | Apolipoprotein C-II |
SAA1 | Serum amyloid A1 |
ORM1 | Alpha-1-acid glycoprotein 1 |
SERPINA1 | Alpha-1-antitrypsin |
HPX | Hemopexin |
TF | Serotransferrin |
ALB | Serum albumin |
CV | Coefficient of variation |
SCX | strong cation exchange |
LC | liquid chromatography |
TFA | trifluoroacetic acid |
HCCA | α-cyano-4-hydroxycinnamic acid |
HPM | Human Proteome Map |
ROC | receiver operating characteristic curve |
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Accession | Protein Name | Protein Class | iTRAQ Ratios | |||
---|---|---|---|---|---|---|
OC/HC + BOT | OC/HC | OC/BOT | BOT/HC | |||
ORM1 | α-1-acid glycoprotein 1 | - | 0.56 | 0.81 | 0.64 | 1.28 |
SERPINA1 | α-1-antitrypsin | Enzyme modulator | 0.75 | 0.48 | 0.89 | 0.54 |
APOC2 | Apolipoprotein C-II | - | 1.24 | 0.96 | 1.67 | 0.59 |
APOC4 | Apolipoprotein C-IV | - | 1.04 | 0.74 | 1.28 | 0.59 |
CRP | C-reactive protein | - | 2.47 | 2.37 | 3.07 | 0.78 |
FGA | Fibrinogen alpha chain | - | 2.31 | 1.97 | 1.83 | 1.09 |
HPX | Hemopexin | Hydrolase | 0.44 | 0.97 | 0.67 | 1.55 |
SERPINA10 | Protein Z-dependent protease inhibitor | Enzyme modulator | 0.98 | 0.76 | 1.20 | 0.60 |
TF | Serotransferrin | Transfer/carrier protein; Receptor; Hydrolase; Defense/immunity protein | 0.64 | 0.91 | 0.65 | 1.39 |
ALB | Serum albumin | Transfer/carrier protein | 0.60 | 0.75 | 0.58 | 1.33 |
SAA1 | Serum amyloid A protein | Transporter; Transfer/carrier protein; Defense/immunity protein | 3.35 | 3.59 | 4.33 | 0.83 |
Protein | OC vs. HC + BOT | OC vs. HC | OC vs. BOT | BOT vs. HC | ||||
---|---|---|---|---|---|---|---|---|
AUC | p-Values | AUC | p-Values | AUC | p-Values | AUC | p-Values | |
ORM1 | 0.518 | 0.4022 | 0.505 | 0.5679 | 0.540 | 0.4580 | 0.536 | 0.6967 |
SERPINA1 | 0.622 | 0.0949 | 0.616 | 0.1091 | 0.627 | 0.2083 | 0.515 | 0.7274 |
APOC2 | 0.621 | 0.1187 | 0.635 | 0.1377 | 0.607 | 0.2330 | 0.523 | 0.6806 |
APOC4 | 0.595 | 0.256 | 0.620 | 0.1769 | 0.569 | 0.5362 | 0.561 | 0.4416 |
CRP | 0.777 | <0.0001 | 0.761 | <0.0001 | 0.793 | <0.0001 | 0.544 | 0.3409 |
HPX | 0.779 | <0.0001 | 0.762 | 0.0011 | 0.796 | <0.0001 | 0.540 | 0.4167 |
SERPINA10 | 0.602 | 0.2756 | 0.559 | 0.5114 | 0.645 | 0.1834 | 0.580 | 0.6550 |
TF | 0.851 | <0.0001 | 0.845 | <0.0001 | 0.858 | <0.0001 | 0.531 | 0.6127 |
ALB | 0.787 | <0.0001 | 0.758 | <0.0001 | 0.875 | <0.0001 | 0.596 | 0.3449 |
SAA1 | 0.825 | <0.0001 | 0.799 | <0.0001 | 0.851 | <0.0001 | 0.593 | 0.1719 |
CA125 * | - | - | - | - | 0.965 | <0.0001 | - | - |
HE4 * | - | - | - | - | 1.0 | <0.0001 | - | - |
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Swiatly, A.; Horala, A.; Matysiak, J.; Hajduk, J.; Nowak-Markwitz, E.; Kokot, Z.J. Understanding Ovarian Cancer: iTRAQ-Based Proteomics for Biomarker Discovery. Int. J. Mol. Sci. 2018, 19, 2240. https://doi.org/10.3390/ijms19082240
Swiatly A, Horala A, Matysiak J, Hajduk J, Nowak-Markwitz E, Kokot ZJ. Understanding Ovarian Cancer: iTRAQ-Based Proteomics for Biomarker Discovery. International Journal of Molecular Sciences. 2018; 19(8):2240. https://doi.org/10.3390/ijms19082240
Chicago/Turabian StyleSwiatly, Agata, Agnieszka Horala, Jan Matysiak, Joanna Hajduk, Ewa Nowak-Markwitz, and Zenon J. Kokot. 2018. "Understanding Ovarian Cancer: iTRAQ-Based Proteomics for Biomarker Discovery" International Journal of Molecular Sciences 19, no. 8: 2240. https://doi.org/10.3390/ijms19082240