Coupled Genome-Wide DNA Methylation and Transcription Analysis Identified Rich Biomarkers and Drug Targets in Triple-Negative Breast Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Sample Datasets Used in the Study
2.2. Analysis of DNA Methylation Data
2.3. Analysis of Gene Expression Data
2.4. Analysis of DMGs and DEGs in Different Regions
2.5. Functional Enrichment Analysis
2.6. Evaluation of Methylation and Expression Biomarkers
2.7. Identification of Potential Drug Targets
3. Results
3.1. Differentially Methylated Genes (DMGs) in TNBC
3.2. Differentially Expressed Genes (DEGs) in TNBC
3.3. Differentially Methylated and Expressed Genes (DMEGs) in TNBC
3.4. DMEGs Predicting TNBCs
3.5. Multiple DMEGs are Potential Druggable Targets
3.6. Structural Basis of Sapropterin Bound to PTGS2
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Groups | Methylation Cut-Off | Expression Cut-Off |
---|---|---|
HypoUp | adjusted p-value < 0.05 and delta β-value < −0.2 | adjusted p value <0.05 and logFC > 2 |
HypoDown | adjusted p-value < 0.05 and delta β-value < −0.2 | adjusted p value <0.05 and logFC < −2 |
HyperUp | adjusted p-value < 0.05 and delta β-value > 0.2 | adjusted p value <0.05 and logFC > 2 |
HyperDown | adjusted p-value < 0.05 and delta β-value > 0.2 | adjusted p value <0.05 and logFC < −2 |
Type | RefGene |
---|---|
Receptors | GPR160, GABRP, RGR, CRHR1, GABBR2, IL1R2, PGR, CHRM3, IL22RA2, BMPR1B, CHRM1 |
Functional Proteins | AGR3, PPP1R14C, ROPN1, OCA2, IGFALS, IGF2BP3, INA, L3MBTL4, SFRP1, FABP7, GPRIN2, S100B, LAMP3, BPI, CNTNAP2, CRABP1, AGR2, PGLYRP2, TMEM74, TMEM150C |
Structural Proteins | TFF1, B3GNT5, KCNK15, LOC145837, FBP1, NCRNA00092, TTC36, ABCC11, LEMD1, C10orf82, ZIC1, C8orf47, POU4F1, DNAH5, CHST4, TTYH1, CXCL1, PROM1, DLX6, ANKRD45, MIA, PYY, LPO, PCOLCE2, CHI3L1, C6orf15, UCHL1, CCDC129, PLCH1, TF, SLC6A15, CORO6, FOXG1, COCH, PTGS2, KRT4, THRSP, WIF1, C1orf64, TFF3, SLC44A4, HPX, STAC, BPIL1, FERMT1, PGBD5, IL20, LRRC17, SLC6A2, KCNS1, CXCL5, HMGCS2, ADD2, SOSTDC1, TLX1, TLX3, KLK10, SPHKAP, DSG1, ANXA8L2, IRX1, UGT2B11, C8orf46, SLC5A1, PRR15, SLC16A6, DNALI1, GSTP1, SPDEF, ST8SIA1, C1QL4, EN1, KCNE4, MUC1, C20orf103, ITGB8, CAPSL, ELF5, LIPG, SOX10, DSC3, CYP4F22, TPSD1 |
RefGene | Region | CpG Sites | DMS | Pattern | Drugs | Drug Examples |
---|---|---|---|---|---|---|
BPI | TSS200 | 3 | 1 | HypoUp | 1 | Fostamatinib |
CHRM1 | Body | 3 | 2 | HypoUp | 95 | Cevimeline, tramadol, succinylcholine |
CHRM3 | Body | 8 | 6 | HyperUp | 75 | Ziprasidone, disopyramide, ipratropium |
GABRP | TSS200 | 3 | 2 | HypoUp | 16 | Prazepam, quazepam, nitrazepam |
TSS1500 | 3 | 1 | HypoUp | 16 | Prazepam, quazepam, nitrazepam | |
GSTP1 | Body | 6 | 4 | HypoUp | 37 | Chlorambucil, cisplatin, busulfan |
PTGS2 | TSS200 | 3 | 3 | HypoUp | 111 | Bufexamac, bendazac, acemetacin |
TSS1500 | 6 | 4 | HypoUp | 111 | Bufexamac, bendazac, acemetacin | |
Body | 5 | 2 | HypoUp | 111 | Bufexamac, bendazac, acemetacin | |
S100B | TSS200 | 2 | 1 | HypoUp | 9 | Olopatadine, calcium, calcium citrate |
SLC6A2 | TSS200 | 3 | 3 | HypoUp | 76 | Amphetamine, phentermine, tramadol |
TF | TSS200 | 3 | 1 | HypoUp | 32 | Cisplatin, isoflurophate, iron dextran |
TSS1500 | 4 | 2 | HypoUp | 32 | Cisplatin, isoflurophate, iron dextran | |
UCHL1 | TSS200 | 2 | 1 | HypoUp | 1 | Phenethyl isothiocyanate |
No. | FDA Drug | Binding Energy (kcal/mol) | No. of Hydrogen Bonds | Residues |
---|---|---|---|---|
1 | Icosapent | −6.63 | 0 | - |
2 | Adapalene | −6.99 | 1 | Gln-192 |
3 | Mesalazine | −6.84 | 1 | Val-523 |
4 | Dapsone | −6.48 | 2 | Gln-192, Ser-530 |
5 | Sapropterin | −6.15 | 6 | Asn-87 (3), His-90, Lys-511, Glu-520 |
6 | Flurbiprofen | −5.88 | 1 | Gln-192 |
7 | Ketorolac | −5.12 | 2 | Arg-513, Val-523 |
8 | Piroxicam | −4.71 | 2 | Ile-517 (2) |
9 | Phenylbutazone | −4.28 | 1 | Arg-513 |
10 | Mefenamic acid | −3.55 | 2 | Met-522, Gln-192 |
11 | Carprofen | −3.19 | 1 | Val-523 |
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Guo, M.; Sinha, S.; Wang, S.M. Coupled Genome-Wide DNA Methylation and Transcription Analysis Identified Rich Biomarkers and Drug Targets in Triple-Negative Breast Cancer. Cancers 2019, 11, 1724. https://doi.org/10.3390/cancers11111724
Guo M, Sinha S, Wang SM. Coupled Genome-Wide DNA Methylation and Transcription Analysis Identified Rich Biomarkers and Drug Targets in Triple-Negative Breast Cancer. Cancers. 2019; 11(11):1724. https://doi.org/10.3390/cancers11111724
Chicago/Turabian StyleGuo, Maoni, Siddharth Sinha, and San Ming Wang. 2019. "Coupled Genome-Wide DNA Methylation and Transcription Analysis Identified Rich Biomarkers and Drug Targets in Triple-Negative Breast Cancer" Cancers 11, no. 11: 1724. https://doi.org/10.3390/cancers11111724