Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis
Abstract
:1. Introduction
2. Methods
2.1. Data Collection and EDC Selection
2.2. Curating Common Interacting Genes between EDCs and Breast Cancer
2.3. Gene Nework Analysis and Screening Potential EDCs
3. Results
3.1. Data Integration
3.2. Finding EDC-Interacting Genes and Mutated Genes in ER Positive Breast Cancer
3.3. Network Analysis of Curated Genes and Potential EDCs
4. Discussion
4.1. What Can Be Derived from the Functional Annotations of the 27 Genes with Regard to Breast Cancer Development?
4.2. How Can Other Potential Diseases be Predicted Based on the 20 Predicted Genes?
4.3. Contributions and Limitations of the Study
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Name (Cas No.) | Interacting Genes |
---|---|
Captan (133-06-2) | 5 genes: GSTP1 | CYP3A4 | ESR1 | NR1I2 | TSC22D1 |
Diethylhexyl Phthalate (117-81-7) | 115 genes: ABCB1 | ACADM | ACADVL | AHR | AKT1 | AMH | AOX1 | AR | ARRDC3 | BAX | BBC3 | BCL2 | CASP3 | CASP7 | CASP8 | CASP9 | CDKN1A | CDO1 | CELSR2 | CGA | CGB3 | CLDN6 | CSNK1A1 | CTNNB1 | CXCL8 | CYP19A1 | CYP1A1 | CYP1B1 | CYP2C19 | CYP2C9 | CYP3A4 | CYP4A10 | DDIT3 | DHCR24 | DIABLO | DNAJB1 | EP300 | ESR1 | ESR2 | FASN |FLG | FSHB | FSHR | GJA1 | GLI3 | GLRX2 | HDAC4 | HDAC5 | HEXA | HEXB | HMGCR | HSD11B2 | HSPA1B | ID1 | IL17RD | IL4 | KLK3 | LAMP3 | LFNG | LHCGR | LIF | MAPK1 | MAPK3 | MARS | MDM2 | MED1 | MMP2 | MMP9 | MTOR | MYC | NCOA1 | NCOR1 | NGB | NR1H3 | NR1I2 | NR1I3 | NR3C1 | NR4A1 | NR4A2 | NR4A3 | PAPSS1 | PAPSS2 |PIK3CA | PMAIP1 | PPARA | PPARB | PPARD | PPARG | PPARGC1A | PRNP | PTCH1 | PTGS2 | RPS6KB1 | RXRA | RXRB | RXRG | SCARA3 | SCD | SLC7A11 | SMO | SP3 | SQLE | SREBF1 | SREBF2 | STAR | SUOX | TIMP2 | TNF | TP53 | TSPAN6 | TXNRD1 | VCL | VEGFA | VLDLR | ZNF461 |
Diethyl Phthalate (84-66-2) | 20 genes: AHR | APOA1 | APOB | AR | CASP3 | CXCL8 | CYP19A1 | CYP1B1 | ESR1 | ESR2 | FLG | NR1I2 | NR1I3 | PPARA | PPARB | PPARG | RXRA | RXRB | RXRG | SHBG |
Lindane (58-89-9) | 134 genes: ABCA1 |ABCB1 | ABCG1 | ABCG2 | ACRC | AGPAT9 | AK4 | ALDH8A1 | AR | ASNS | BAX | BCL2 | BCL6 | BIRC3 | BRCA1 | C15ORF39 | CARS | CAT | CCND1 | CCNG2 | CD69 | CD84 | CDKN1A | CEBPB | CHAC1 | CRIM1 | CX3CR1 | CYP11A1 | CYP11B1 | CYP11B2 | CYP17A1 | CYP19A1 | CYP1A1 | CYP2B6 | CYP2D6 | CYP2E1 | CYP3A4 | CYP3A7 | DAP3 |DNAJB4 | DUSP10 | ERBB2 | ERBB3 | ESR1 | ESR2 | ESRRA | EVI2A | FAM107B | FAM213B | FBXO32 | FRAT1 | GABRA1 | GABRA2 | GABRA4 | GABRA6 | GABRB1 | GABRB2 | GABRB3 | GABRG2 | GABRR1 | GCLC | GCLM | GLRA1 | GLRA2 | GLRA3 | GNRH1 | GPR18 | GPT2 | GSR | GSTM1 | HMGCS1 | HSD3B2 | HSPA1A | HYLS1 | ID1 | IER3 | IFNG | IL5 |ISL2 | JUN | KIF21B | KLHL24 | LIF | MAP2K1 | MAP2K2 | MAPK1 | MAPK3 | MMP9 | MTHFD2 | NANOS1 | NCOA7 | NFE2L3 | NOS2 | NR1I2 | NRF1 | PDCD4 | PELI1 | PGR | PLCL1 | PNRC1 | POMC | PPARGC1A | PPRC1 | RAF1 | RARA | RGS2 | RXRB | SEMA3G | SESN2 | SGK1 | SHBG | SLC10A1 | SLC22A1 | SLC3A2 | SLC7A11 | SQSTM1 | SRC | SRXN1 |STAM2 | STAR | SULT2A1 | TFAM | TFB2M | TFF1 | TM6SF1 | TMCO6 | TMEM177 | TMEM267 | TNF | TP53 | TRIB3 | VEGFA | VLDLR | ZNF628 |
Degree Centrality | Gene | Official Full Name | Interacting Gene | Networks * |
---|---|---|---|---|
13 | ESR1 | Estrogen receptor 1 | AKT1 | 2 |
AR | 2, 3, 5, 6 | |||
BRCA1 | 2, 3 | |||
CASP8 | 7 | |||
EP300 | 2, 3 | |||
ERBB2 | 2 | |||
HDAC5 | 2 | |||
NCOA1 | 2, 3 | |||
NCOA7 | 2, 3 | |||
PIK3CA | 2, 3 | |||
SLC10A1 | 1 | |||
SMO | 1 | |||
TP53 | 2 | |||
12 | TP53 | Tumor protein p53 | AKT1 | 1 |
AR | 2, 7 | |||
BCL6 | 2, 3 | |||
BRCA1 | 2, 3 | |||
CASP8 | 2 | |||
EP300 | 2, 7 | |||
ERBB2 | 1 | |||
ESR1 | 2 | |||
HDAC5 | 2 | |||
MTOR | 2 | |||
NCOA1 | 2 | |||
SMO | 1 | |||
12 | NCOA1 | Nuclear receptor coactivator 1 | AKT1 | 1, 3 |
AR | 2, 3 | |||
BRCA1 | 2 | |||
CYP1A1 | 1 | |||
DUSP10 | 1, 7 | |||
EP300 | 1, 2, 3, 6 | |||
ESR1 | 2, 3 | |||
HDAC5 | 7 | |||
KLHL24 | 1 | |||
NCOA7 | 7 | |||
PTCH1 | 7 | |||
TP53 | 2 | |||
11 | AKT1 | AKT serine/threonine kinase 1 | AR | 2 |
BRCA1 | 2 | |||
EP300 | 2 | |||
ERBB2 | 1 | |||
ESR1 | 2 | |||
MAP2K2 | 1 | |||
MTOR | 2, 3, 5, 4 | |||
NCOA1 | 1, 3 | |||
PIK3CA | 2, 3 | |||
SMO | 3 | |||
TP53 | 1 | |||
11 | BCL6 | B-cell CLL/lymphoma 6 | ABCG1 | 7 |
APOB | 1, 7 | |||
EP300 | 2, 7 | |||
GABRR1 | 7 | |||
HDAC5 | 2, 3 | |||
KLHL24 | 1 | |||
PIK3CA | 1 | |||
PTCH1 | 7 | |||
SLC10A1 | 1 | |||
SMO | 2 | |||
TP53 | 2, 3 |
Score | Chemical Name (Cas No.) | Interacting Genes |
---|---|---|
40 | Perfluorooctanoic acid (335-67-1) | ABCG1, APOB, CYP1A1, ERBB2, ESR1, TP53, SHH |
37 | Stearic acid (57-11-4) | ABCG1, AKT1, AR, ESR1 |
35 | Triphenyl phosphate (115-86-6) | AR, ESR1, TP53 |
34 | Dibutyl Phthalate (84-74-2) | AKT1, AR, ESR1 |
30 | Sodium Fluoride (7681-49-4) | AKT1, CASP8, TP53, FAS |
GO Term | Ontology Source | p-Value | Annotated Genes |
---|---|---|---|
Proteoglycans in cancer | KEGG | 4.0 × 10−14 | AKT1|BRAF|ERBB2|ESR1|FAS|MAP2K2| MTOR|PIK3CA|PTCH1|SHH|SMO|TP53 |
Thyroid hormone signaling pathway | KEGG | 7.2 × 10−12 | AKT1|EP300|ESR1|MAP2K2|MTOR|NCOA1| PIK3CA|RHEB|TP53 |
Regulation of transcription from RNA polymerase III promoter | GO-Biological process | 1.6 × 10−8 | AR|BRCA1|ERBB2|MTOR|RPTOR |
Mammary gland epithelium development | GO-Biological process | 2.5 × 10−8 | AKT1|AR|ESR1|PML|PTCH1|SMO |
Positive regulation of transcription from RNA polymerase III promoter | GO-Biological process | 2.8 × 10−8 | AR|ERBB2|MTOR|RPTOR |
Cholesterol efflux | GO-Biological process | 5.0 × 10−8 | ABCG1|ABCG4|APOB|PTCH1|SHH |
Regulation of protein deacetylation | GO-Biological process | 3.0 × 10−6 | BCL6|EP300|PML|TP53 |
T cell selection | GO-Biological process | 2.0 × 10−4 | BRAF|FAS|SHH |
Labyrinthine layer development | GO-Biological process | 2.6 × 10−4 | AKT1|CASP8|NCOA1 |
Response to antibiotic | GO-Biological process | 3.4 × 10−4 | CASP8|CYP1A1|TP53 |
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Jeong, H.; Kim, J.; Kim, Y. Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis. Int. J. Environ. Res. Public Health 2017, 14, 1158. https://doi.org/10.3390/ijerph14101158
Jeong H, Kim J, Kim Y. Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis. International Journal of Environmental Research and Public Health. 2017; 14(10):1158. https://doi.org/10.3390/ijerph14101158
Chicago/Turabian StyleJeong, Hyeri, Jongwoon Kim, and Youngjun Kim. 2017. "Identification of Linkages between EDCs in Personal Care Products and Breast Cancer through Data Integration Combined with Gene Network Analysis" International Journal of Environmental Research and Public Health 14, no. 10: 1158. https://doi.org/10.3390/ijerph14101158