Scientists from the Northwestern University have identified a biomarker strongly associated with basal-like breast cancer, a highly aggressive carcinoma that is resistant to many types of chemotherapy. The biomarker, a protein called STAT3, provides a smart target for new therapeutics designed to treat this often deadly cancer.
Using breast cancer patient data taken from The Cancer Genome Atlas the team used powerful computational and bioinformatics techniques to detect patterns of gene expression in two cancer subtypes. They found that a small number of genes are activated by STAT3 protein signalling in basal-like breast cancers but not in luminal breast cancers.
Basal-like cancer is a category that includes a number of different breast cancers, including the highly aggressive form called triple negative cancer. The researchers stated that breast cancer can’t be treated as one disease. And described cancer as many molecular processes that have gone wrong. The team teased out from large amounts of data that STAT3 activity correlates with distinct patterns of gene expression in one type of breast cancer but not in another. The findings are published in the the journal Proceedings of the National Academy of Sciences (PNAS).
The results suggest a clinical study should be conducted of a STAT3-inhibiting drug in patients with basal-like and luminal cancers. Currently there are no pills or injections targeting STAT3 for breast cancer patients.
Previous research has found the STAT3 protein to be overactive in many breast cancers, but its role has not been well understood. The current study is the first to compare breast cancer subtypes and gene expression patterns associated with STAT3 in the tumours of human patients.
The team observed that there are many clearly visible patterns of common gene expression, where certain genes are turned on and certain genes are turned off, in the basal-like cancers. Those clear patterns were not seen in the luminal cancers.
This opens up the possibility that cancer subtype-specific signalling is driven by STAT3 and that STAT3 inhibitors may be more effective in patients diagnosed with basal-like cancers than in those with luminal cancers.
STAT3 stands for signal transducer and activator of transcription 3, a transcription factor (a protein) encoded by the STAT3 gene in humans. In addition to its known roles in cancerous cells, STAT3 also is an essential mediator of cytokine and growth factor signals in normal cells that are important for diverse processes including immunity and inflammation.
The team identified 84 genes that are expressed differently in basal-like cancer tumours as compared to luminal cancer tumours. These genes are highly representative of the immune response and inflammation processes and consistent with the role of STAT3.
The intensive analysis used data from 825 breast cancer patients from across the country, each with hundreds of data points. The data included protein expression, protein phosphorylation, which indicates which signalling pathways are activated, and messenger RNA and microRNA expression.
To sort through the vast amounts of data, the researchers took advantage of Quest, a high-performance computing system at Northwestern. The computer cluster they used offered the equivalent of the processors and random-access memory (RAM) of eight powerful desktop computers linked together.
The group emphasized that this is a statistical analysis and the findings need to be verified with careful laboratory and clinical experiments. The team now plans to conduct such a study.
Source: Northwestern University