To read the full study, please see Oncotarget Volume 8 issue 13 | Systematic functional perturbations uncover a prognostic genetic network driving human breast cancer – Dr. Tristan Gallenne, et al.
Dr. Ramaswamy from Harvard and Dr. Peeper of The Netherlands Cancer Institute have investigated a set of genes that form a network, one that includes several potential targets for therapy in women with breast cancer.
Gene expression patterns of primary breast cancers help clinicians to predict the risk of metastatic disease and some prognostic signatures have been recently validated which highlight their clinical value. It allows doctors to answer some vital questions for patients, including the chance of recurrence and the rate of progression of the disease.
In a previous study from 2013, the researchers found that a transcription factor called Fra-1 is a key promoter of breast cancer cell metastasis. Fra-1 also was found to be a good predictor of clinical outcome of patients. Their current study sought to further analyze Fra-1 and its role in breast cancer development.
The team of scientists selected genes that were highly expressed in poor-prognosis breast cancer patients, producing a set of 31 genes. Using 2317 breast cancer gene-expression profiles from publicly available datasets, the scientists determined that this 31-gene set is significantly related to the clinical outcome of breast cancer patients.
Of the 31 genes 7 were cytotoxic (lethal to cells) and were not used in the experiment because they may confound the results. Of the remaining 24 poor prognostic genes, depleting nine of them reduced metastasis and greatly increased the survival rate in the experimental mice
They found that getting rid of nine of these genes greatly prolonged survival in laboratory mice by reducing metastatic disease. This shows us that the nine-gene set is required for breast cancer growth and aggressiveness. Interestingly, these nine genes have seemingly unrelated functions but do in fact communicate with one another. Their expression is regulated by the same three sex hormones, estrogen amongst them.
Dr. Ramaswamy, Dr. Peeper and their teams have proposed, for the first time, a key group of genes in poor-prognosis patients; previous research had focused only on good-prognosis patients. This data allow doctors to identify patients who are associated with poor-prognosis, then treat them with one or more inhibitory agents targeting the nine-gene set. These findings contribute toward a more personalized management of poor-prognosis breast cancer patients.
Funding: This study was funded by awards from the National Cancer Institute and Stand-Up-To-Cancer; by the Dutch Cancer Society (KWF Kankerbestrijding), by A Sister’s Hope grant and a donation by (Z)aan aan de Wandel.
Q. In response to an article out of Oncotarget Volume 8 Issue 13, where scientists present a nine-gene set relevant to poor-prognosis breast cancer patients – Do these nine genes control all types of breast cancer?
A. No. These nine genes are found to be expressed highly in poor-prognosis patients specifically, or patients that have a slim chance of recovery. When these nine genes were depleted, survival was extended. Doctors may now be able to identify poor-prognosis patients, then treat them with agents that inhibit this nine-gene set.
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