2024-04-23 ジョージア工科大学
<関連情報>
- https://research.gatech.edu/georgia-tech-researchers-identify-novel-gene-networks-associated-aggressive-type-breast-cancer
- https://www.liebertpub.com/doi/10.1089/genbio.2024.0002
- https://www.cell.com/iscience/fulltext/S2589-0042(21)01493-0
乳がんの発症と進展における遺伝子ネットワーク相互作用の変化 Changes in Gene Network Interactions in Breast Cancer Onset and Development
Zainab Arshad, Stephen N. Housley, Kara Keun Lee, and John F. McDonald
GEN Biotechnology Published:18 April 2024
DOI:https://doi.org/10.1089/genbio.2024.0002
Abstract
While cancer is generally recognized as a polygenic disease, specific “driver genes” have been identified as promising candidates for targeted gene therapy. While this precision approach has, in many cases, dramatically improved patient treatments/outcomes, much remains to be learned about the molecular basis of cancer. Recent evidence indicates that changes underlying cancer onset/progression are not only attributable to changes in DNA structure/expression of individual genes but to changes in interactions among genes as well. Gene co-expression network analysis can provide novel insight into gene–gene interactions associated with important biological processes involved in cancer that go undetected in standard genetic analyses and may help identify promising new targets for cancer therapy. RNA-seq count data of breast cancer subtypes (Luminal A, Luminal B, and Basil-like) and healthy breast tissues were employed in our analysis. The Basal-like subtype displayed the most highly connected network structure but was the most dissimilar of the three subtypes relative to normal controls. Many network modules were completely lost in the Basal-like subtype, while being preserved in both the Luminal A and Luminal B networks. Forty modules were unique to the Basel-like subtype. Survival analysis of Basal-like modules uncovered 19 genes enriched for functions previously identified as “Hallmarks of Cancer.” Unexpectedly, several neural pathways not previously associated with breast cancer were identified as being unique to the Basal-like subtype. Our findings demonstrate the utility of network analysis in the identification of potential new candidates for breast cancer diagnostics and targeted gene therapy.
がんの発症と進行に関連する遺伝子間相互作用の変化は、遺伝子発現の変化とはほとんど無関係である Changes in gene-gene interactions associated with cancer onset and progression are largely independent of changes in gene expression
Zainab Arshad,John F. McDonald
iScience Published:November 25, 2021
DOI:https://doi.org/10.1016/j.isci.2021.103522
Highlights
- Gene-gene network complexity is reduced in the transition from normal to cancer
- Network similarity across cancer types is higher in early-stage versus late-stage cancers
- Network interactions among housekeeping genes are stable through cancer development
- <10% of changes in network interactions in cancer involve changes in gene expression
Summary
Recent findings indicate that changes underlying cancer onset and progression are not only attributable to changes in DNA structure and expression of individual genes but to changes in interactions among these genes as well. We examined co-expression changes in gene-network structure occurring during the onset and progression of nine different cancer types. Network complexity is generally reduced in the transition from normal precursor tissues to corresponding primary tumors. Cross-tissue cancer network similarity generally increases in early-stage cancers followed by a subsequent loss in cross-tissue cancer similarity as tumors reacquire cancer-specific network complexity. Gene-gene connections remaining stable through cancer development are enriched for “housekeeping” gene functions, whereas newly acquired interactions are associated with established cancer-promoting functions. Surprisingly, >90% of changes in gene-gene network interactions in cancers are not associated with changes in the expression of network genes relative to normal precursor tissues.
Graphical abstract
