Two genes linked to breast cancer survival

Two key genes capable of predicting 10-year disease-specific survival outcomes in breast cancer patients have been identified by researchers at the Institute of Cancer Research (ICR) in London.

Published in the journal Oncotarget, the recent study of a cohort of 1964 patients suggests that the genes F12 and STC2 influence the interaction and adhesion of cancer cells to the protein laminin. This constitutes an important part of the extracellular matrix (ECM) that is the 'anchor' that keeps cancer cells from spreading through blood and lymphatic vessels to other organs of the body. If breast cancer cells migrate and spread around the body, this can result in patient death.

Professor Paul Workman, chief executive of the ICR, said: 'We have seen major strides in the treatment of breast cancer, but once it begins to spread round the body it is still often fatal. This new study helps us understand some of the processes that control how breast cancers spread, and identifies a pattern of genetic activity that could be used to pick out women particularly at risk.'

Researchers used a newly developed image-based in vitro screening technique to identify breast cancer cells containing the protein HER-2, where the cells did not adhere to the ECM. HER-2 is found in one-fifth of breast cancer tumours. This led to the identification of the genes STC2 and F12 as independent prognostic factors.

STC2 encodes the protein stanniocalcin 2, and reduced expression of STC2 impairs laminin adhesion and results in enhanced breast cancer cell growth and migration. STC2 is therefore a positive indicator for disease-free survival.

F12, which codes for the blood plasma coagulation factor XII, also potently induces cell division, leading to the proliferation of cancer cells. This study is the first to announce F12 as a negative indicator for overall survival and as a potential therapeutic target.

The researchers categorised patients into four prognostic subgroups, according to the expression of the two genes. F12-high/STC2-low tumours were associated with the poorest outcome of a 32 percent chance of death within ten years. The lowest chance (ten percent) was reported for F12-low/STC2-high tumours.        

Dr Paul Huang, leader of the Protein Networks Team at the ICR, said: 'If the results are confirmed in larger studies, it could give us a new way of assessing women's survival chances in the clinic, and adjusting treatment accordingly.'