Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis
As key inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL6) play an important role in the pathogenesis of non-inflammatory diseases, including specific cancers, such as breast cancer (BC). Previous genome-wide association studies (GWASs) have neither explained the large proportio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/9/1379 |
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| author | Su Yon Jung Jeanette C. Papp Matteo Pellegrini Herbert Yu Eric M. Sobel |
| author_facet | Su Yon Jung Jeanette C. Papp Matteo Pellegrini Herbert Yu Eric M. Sobel |
| author_sort | Su Yon Jung |
| collection | DOAJ |
| description | As key inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL6) play an important role in the pathogenesis of non-inflammatory diseases, including specific cancers, such as breast cancer (BC). Previous genome-wide association studies (GWASs) have neither explained the large proportion of genetic heritability nor provided comprehensive understanding of the underlying regulatory mechanisms. We adopted an integrative genomic network approach by incorporating our previous GWAS data for CRP and IL6 with multi-omics datasets, such as whole-blood expression quantitative loci, molecular biologic pathways, and gene regulatory networks to capture the full range of genetic functionalities associated with CRP/IL6 and tissue-specific key drivers (KDs) in gene subnetworks. We applied another systematic genomics approach for BC development to detect shared gene sets in enriched subnetworks across BC and CRP/IL6. We detected the topmost significant common pathways across CRP/IL6 (e.g., immune regulatory; chemokines and their receptors; interferon γ, JAK-STAT, and ERBB4 signaling), several of which overlapped with BC pathways. Further, in gene–gene interaction networks enriched by those topmost pathways, we identified KDs—both well-established (e.g., JAK1/2/3, STAT3) and novel (e.g., CXCR3, CD3D, CD3G, STAT6)—in a tissue-specific manner, for mechanisms shared in regulating CRP/IL6 and BC risk. Our study may provide robust, comprehensive insights into the mechanisms of CRP/IL6 regulation and highlight potential novel genetic targets as preventive and therapeutic strategies for associated disorders, such as BC. |
| first_indexed | 2024-03-10T07:52:27Z |
| format | Article |
| id | doaj.art-96ae834c14a646cc93fe9134650b7d5a |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T07:52:27Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-96ae834c14a646cc93fe9134650b7d5a2023-11-22T12:11:47ZengMDPI AGBiomolecules2218-273X2021-09-01119137910.3390/biom11091379Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems AnalysisSu Yon Jung0Jeanette C. Papp1Matteo Pellegrini2Herbert Yu3Eric M. Sobel4Translational Sciences Section, School of Nursing, University of California, Los Angeles, CA 90095, USAJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USADepartment of Molecular, Cell and Developmental Biology, Life Sciences Division, University of California, Los Angeles, CA 90095, USACancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI 96813, USADepartment of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USAAs key inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL6) play an important role in the pathogenesis of non-inflammatory diseases, including specific cancers, such as breast cancer (BC). Previous genome-wide association studies (GWASs) have neither explained the large proportion of genetic heritability nor provided comprehensive understanding of the underlying regulatory mechanisms. We adopted an integrative genomic network approach by incorporating our previous GWAS data for CRP and IL6 with multi-omics datasets, such as whole-blood expression quantitative loci, molecular biologic pathways, and gene regulatory networks to capture the full range of genetic functionalities associated with CRP/IL6 and tissue-specific key drivers (KDs) in gene subnetworks. We applied another systematic genomics approach for BC development to detect shared gene sets in enriched subnetworks across BC and CRP/IL6. We detected the topmost significant common pathways across CRP/IL6 (e.g., immune regulatory; chemokines and their receptors; interferon γ, JAK-STAT, and ERBB4 signaling), several of which overlapped with BC pathways. Further, in gene–gene interaction networks enriched by those topmost pathways, we identified KDs—both well-established (e.g., JAK1/2/3, STAT3) and novel (e.g., CXCR3, CD3D, CD3G, STAT6)—in a tissue-specific manner, for mechanisms shared in regulating CRP/IL6 and BC risk. Our study may provide robust, comprehensive insights into the mechanisms of CRP/IL6 regulation and highlight potential novel genetic targets as preventive and therapeutic strategies for associated disorders, such as BC.https://www.mdpi.com/2218-273X/11/9/1379CRP/IL6breast cancermulti-omics integrationsystem biologymolecular pathwaysgene network |
| spellingShingle | Su Yon Jung Jeanette C. Papp Matteo Pellegrini Herbert Yu Eric M. Sobel Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis Biomolecules CRP/IL6 breast cancer multi-omics integration system biology molecular pathways gene network |
| title | Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis |
| title_full | Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis |
| title_fullStr | Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis |
| title_full_unstemmed | Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis |
| title_short | Molecular Biology Networks and Key Gene Regulators for Inflammatory Biomarkers Shared by Breast Cancer Development: Multi-Omics Systems Analysis |
| title_sort | molecular biology networks and key gene regulators for inflammatory biomarkers shared by breast cancer development multi omics systems analysis |
| topic | CRP/IL6 breast cancer multi-omics integration system biology molecular pathways gene network |
| url | https://www.mdpi.com/2218-273X/11/9/1379 |
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