Two genes in breast cancer tumors may indicate an increased risk of death, suggests a new study published in Oncotarget.
For the study, researchers led by Paul H Huang, looked at breast cancer cells positive for human epidermal growth factor receptor 2, a mutation found in ~20% of tumors and one that is often targeted by modern therapeutics. The researchers believed that certain genes in these breast cancer tumors could play a role in helping to release cancerous cells from the extracellular matrix and spread to other regions in the body.
Using a new image-based screening technique, they identified cancerous cells that did not stick to the protein laminin—which helps to manage disease progression—and found those cells tended to have high activity in a gene called F12 and low activity in one called STC2. An analysis of 1964 breast cancer samples then revealed that this pattern strongly correlated with survival.
Women whose tumors had a high expression of F12 and a low expression of STC2 had a 32% chance of dying within 10 years, while those with low F12 activity and high STC2 activity had only a 10% chance of dying within the same timeframe.
Therefore, researchers concluded that laminin itself is not a prognostic indicator of disease-free or overall survival, but that F12 and STC2 activity derived from a gene expression signature of impaired laminin adhesion are prognostic factors for overall survival in breast cancer. More research is needed to establish how these genes interfere with the extracellular matrix, helping cancer cells grow and spread.
“Survival rates for breast cancer are now much higher than they were a few decades ago, but the disease remains deadly once it has spread round the body,” said Dr Haung. “Our study sheds light on how cancer cells unstick themselves from healthy tissue, and it could help pick out women at high risk of their cancer spreading and becoming fatal.”
However, he and his colleagues did note that one limitation of their study was that all adhesion measurements were performed on extracellular matrix-coated surfaces as opposed to 3-dimensional culture systems, which better simulates the tumor microenvironment. They anticipate more studies using 3-dimension cultures to be conducted, which could help to identify additional independent adhesion-associated prognosticators of breast cancer survival.
