Georgia Tech researchers discover new gene network linked to aggressive breast cancer

Georgia Tech researchers discover new gene network linked to aggressive breast cancer

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Breast cancer is the second most common cancer diagnosis among American women and the second leading cause of cancer death in women. Breast cancer treatment has improved significantly in recent years thanks to targeted gene therapy and immunotherapy. However, this approach is less successful for a small group of patients diagnosed with the most aggressive form of basaloid breast cancer.

Recently, scientists have Georgia Institute of Technology Comprehensive Cancer Research Center (ICRC) The researchers found that this particular breast cancer exhibits a unique network structure of interacting genes. The researchers used a mathematical model called graph theory to simulate the relationship between a pair of objects and computationally detected changes in gene-gene interactions: The development and progression of this type of breast cancer.

The discovery of a new gene network associated with basaloid breast cancer helps us identify potential new gene targets for the treatment of this very aggressive form of breast cancer,” john macdonaldFounding Director of the International Committee of the Red Cross, Honorary Professor of the School of Biological Sciences, and corresponding author of this study. We would not have discovered these potential treatments through gene expression analysis alone.

Although accounting for only 10-20% of breast cancer diagnoses, basaloid breast cancer is more aggressive than other subtypes and, if not caught early, may be treated with effective anti-cancer drugs when it can be treated with surgery and/or radiation therapy. Can cause breast cancer. The basal-like subtype does not respond to conventional hormonal therapy.

a theory Why, many cancer researchers argue, can’t a single gene act autonomously? Therefore, changes in gene interactions in cancer may be as important as the cancer driver genes themselves.

MacDonald said the components of any complex system, such as the human genome, are certainly important. The way these individual components interact with each other is also critical.

In this study, researchers analyzed the three main subtypes of breast cancer, with a special emphasis on the most aggressive basal-like subtype. The researchers found that the gene-gene interaction network in the aggressive basal-like subtype is significantly different compared with the more common luminal A and luminal B subtypes.

Many of the genes that make up these unique networks were found to be involved in functions not previously associated with breast cancer. Stephen Housley“An unexpected and interesting result of our study is that neural processes appear to play an important role in differentiating highly aggressive basaloid tumors from non-basaloid tumors,” said a researcher in neurobiology in the School of Biological Sciences and a co-author of the paper. effect.

In total, the researchers examined more than 300 million pairs of genes, comparing healthy women with breast cancer patients. Study co-author Zainab Ashard is a computational biologist who most recently worked in McDonald’s lab. explained that differences in gene network structure between healthy individuals and breast cancer patients allow us to identify changes in gene-gene interaction patterns during breast cancer development.[s1]

The team’s findings are detailed in a new paper, “Changes in Gene Network Interactions in Breast Cancer Initiation and Development,” published in April 2024 issue Gene Biotechnology. Based on the results of this study and their previously published analysis of eight other types of cancer, the researchers believe they have identified the utility of network analysis in identifying potential new candidates for diagnosis and targeted gene therapy in breast cancer and other types of cancer. Usefulness.

In addition to McDonald, Housley and Ashard, former bioinformatics Ph.D. Kara Keun Lee also participated in the research. Students working in McDonald’s lab are also co-authors on the paper.

The results presented here are based in whole or in part on data generated by the TCGA research network. The Genotype-Tissue Expression (GTEx) project is supported by the NIH Office of the Director Common Fund and NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS.

This research was supported by the Mark Wright Comprehensive Cancer Research Center Student Fellowship, the Deborah Nash Endowment, Northside Hospital (Atlanta), and the Ovarian Cancer Research Institute (Atlanta).

Citation: Changes in gene network interactions in breast cancer initiation and progression, Zainab Arshad, Stephen N. Housley, Kara Keun Lee, and John F. McDonald, GEN Biotechnology, April 2024,
DOI: https://doi.org/10.1089/genbio.2024.0002

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