Applications of Proteomics in Ovarian Cancer: Dawn of a New Era
Abstract
:1. Introduction
2. Signaling Pathways in OC
3. Proteomic Biomarkers for OC
3.1. Tissue Proteomics
3.2. Proteomics of Post-Translational Modifications
3.3. Quantitative Proteomics
3.4. Biofluid Proteomics
4. Proteomic Techniques
4.1. Two-Dimensional Gel Electrophoresis (2DE)
4.2. MS-Based Techniques
4.2.1. MALDI-TOF
4.2.2. SELDI-TOF
4.3. Protein Microarrays
4.4. Mitochondrial Proteomics Methods
5. New Approaches in Proteomics
5.1. Targeted Proteomics
5.2. Peptidomics
5.3. Exosomes
6. Proteomics in the Treatment of Ovarian Cancer
6.1. Tackling Chemotherapy Resistance
6.2. Targeted Therapy Using Proteomics
7. PARP Inhibitors
8. VEGF/VEGF Receptor Inhibitors
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Approval Status | Biomarker | Sample | Sensitivity | Specificity | References | Discovery |
---|---|---|---|---|---|---|
FDA approved biomarkers | CA125 | Serum/Plasma | 60–70% | 94% | [15,61,62,63] | Immunoassay-1981 |
HE4 | Serum/Plasma/Urine | 72.9% | 94% | [61,64,65,66] | ctDNA arrays, Immunoassay-2008 | |
CancerSEEK | Blood | 98% | 99% | [63,67] | ctDNA, Multiplex PCR assays, others | |
ROMA | Serum | 79% | 78% | [15,63,68] | Immunoassays, Menopausal status-2010 | |
OVA1 (Transthyretin, β-2 microglobulin, CA125, transferrin and apolipoprotein A1) | Blood | 94% | 54% | [61,69] | Multivariate Immunoassay-2009 | |
OVERA (HE4, FSH, CA125, transferrin and apolipoprotein A1) | Blood | 91–94% | 69% | [15,61,63] | Multivariate Immunoassay-2016 | |
Other biomarker candidates | Anti-TP53, TRIM-21, NY-ESO-1 (CTAG-1A) and PAX-8 | Serum | 46–67% | 94–98% | [63,70] | PCR, line BLOT, ctDNA, Western blot, ELISA |
HE4 antigen-autoantibody complexes with CA125 | Serum | 38% alone 60–80% when combined | 98% | [63,71] | Multiplexed Immunoassay | |
MiRNAs (multiple) | Tumour/Serum/Plasma | Negative predictive value 78.6% | Positive predictive value 91.3% | [63,72,73] | Microarrays, PCR | |
Kallikrein | Serum | 21–26% | 94% | [74] | PCR, Densitometry, DNA sequencing | |
APC, RASSF1A, CHDH1, RUNX3, TFP12, SRP5 and OPCML | Serum | 85% | 91% | [63,75] | DNA methylation, PCR | |
CA125, osteopontin, macrophage inhibitory factor and anti-IL8 autoantibodies | Serum | 82% | 98% | [63,76] | Multiplexed immunoassay | |
CA125, apolipoprotein B, transthyretin | Serum | 74% | 97% | [77] | SELDI TOF, immunoassay |
Biomarker | Discovery | Sample | No. of Patients | No. of Controls | Sensitivity | Specificity | References |
---|---|---|---|---|---|---|---|
CA125, C-Reactive protein, Serum amyloid A, IL-6, IL-8 | Multiplexed assay | Plasma | 150 | 212 | 94% | 91% | [78] |
Four lipid metabolites | LC-MS | Plasma | 50 | 50 | 95% | 35% | [79] |
CA125, HE4, CA72.4, and CA15.3 (European EPIC cohort) | Immunoassay | Blood | 810 | 1939 | 95% | 98% | [80] |
c17orf64, IRX2, TUBB6 | Genome-wide methylation analysis, qMSP assays | Tissue | 23 | 36 | 100% | 100% | [81] |
92 proteins (CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN, ADAM8 were significant) | Multi assay | Blood | 91 | 180 | AUC > 0.70 for the 9 proteins | Not reported | [82] |
metabolites | UPLC-MS | Plasma | 140 | 308 | Not reported | Not reported | [83] |
TRIM21, NY-ESO-1, TP53, PAX8 | ELISA, Western Blot | Serum | 114 | 50 | 46–67% | 94–98% | [70] |
miR-1246, miR-595, miR-2278 | Microarray, RT-qPCR | Serum/Tissue | 168 | 65 | 87% | 77% | [84] |
10-miRNA profile (miR-320a, miR-665, miR-3184-5p, miR-6717-5p, miR-4459, miR-6076, miR-3195, miR-1275, miR-3185, miR-4640-5p) | Microarray | Serum | 428 | 2759 | 99% | 100% | [85] |
HE4 autoantibody | Immunoassay | Serum | 145 | 212 | 38% alone, 60–80% when combined | 98% | [71] |
lncRNAs | Microarray, qPCR | Tissue | 18 | 31 | Not reported | Not reported | [86] |
Biomarkers | References | |
---|---|---|
Protein antigen | CA125, HE4, CA72.4, CA15-3, CEA and V-CAM1 Glycodelin, E-cadherin and IL-639 or transthyretin | [63] |
Immune related-Cytokine, chemokine | IL-6, IL-7, IL-8, IL-12, B7-H3, B7-H4 interferon-γ, auto antibodies against TP53, TRIM-21, NY-ESO-1 (CTAG-1A), PAX-8 | [63,87] |
Signalling molecule | EGFR, HER2, p53 mutaion, cyclin D1, cyclin E, sFas | [87] |
Inherited gene mutations | BRCA1, BRCA2 MSH2, MLH1, MSH6, PMS2 RAD51C, RAD51D, BRIP1, BARD1, CHEK2, MPE11A, NBN, PALB2, RAD50, TP53 | [88] |
Gene expression | CA125, osteopontin, kallikrein 10, secretory leukoprostease inhibitor, matrix metalloproteinase-7 FOL3, survivin, MCM3, E2Fs, VTCN1, SYNE1, AKAP14, KNDC1, DLEC1 ovarian cancer prognostic profile (115 gene signature) ctDNA: APC, RASSF1A, CHDH1, RUNX3, TFP12, SRP5, OPCML | [89,90] |
Angiogenesis | VEGF, FGF-1, Claudin-3, claudin-7, EZH2, EphA2 | [87] |
Epigenetic changes | Hypermethylation: BRCA1, RASSF1A, APC, p14ARF, p16INK4a, DAPKinase59 ARMCH1, ICAM4, LOC134466, PEG3, PYCARD SGNE160 MiRNAs: miR-200a, miR-141, miR-199a, miR-140, miR-145, miR-125b163 miR-18266, miR-21, miR-92, miR-93, miR-126, miR-29a, miR-155, miR-127, miR-99b68 | [88] |
Protein antigen | CA125, HE4, CA72.4, CA15-3, CEA and V-CAM1 Glycodelin, E-cadherin, IL-639, or transthyretin. | [63] |
Biomarkers | Techniques | Reference |
---|---|---|
Annexin3, Destin | MALDI-TOF | [44] |
ERp57 | MALDI-TOF, ESI-Q-TOF | [44] |
Activated Leucocyte Cell Adhesion Molecule, Nestin | Orbitrap | [44] |
Pyruvate kinase isozymes M1/M2 Heat shock protein family D | ESI-Q-TOF | [44] |
Abbreviation: ESI-Q-TOF; Electrospray-ionisation quadrupole time-of-flight mass spectrometry |
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Ghose, A.; Gullapalli, S.V.N.; Chohan, N.; Bolina, A.; Moschetta, M.; Rassy, E.; Boussios, S. Applications of Proteomics in Ovarian Cancer: Dawn of a New Era. Proteomes 2022, 10, 16. https://doi.org/10.3390/proteomes10020016
Ghose A, Gullapalli SVN, Chohan N, Bolina A, Moschetta M, Rassy E, Boussios S. Applications of Proteomics in Ovarian Cancer: Dawn of a New Era. Proteomes. 2022; 10(2):16. https://doi.org/10.3390/proteomes10020016
Chicago/Turabian StyleGhose, Aruni, Sri Vidya Niharika Gullapalli, Naila Chohan, Anita Bolina, Michele Moschetta, Elie Rassy, and Stergios Boussios. 2022. "Applications of Proteomics in Ovarian Cancer: Dawn of a New Era" Proteomes 10, no. 2: 16. https://doi.org/10.3390/proteomes10020016