Scientists identify biomarker strongly associated with aggressive breast cancer -
Two scientists at Northwestern University have identified a biomarker strongly associated with basal-like breast cancer, very aggressive cancer that is resistant to many types of chemotherapy. The biomarker, a protein called STAT3, provides intelligent target for new therapeutics to treat this often lethal cancer.
Using breast cancer patient data taken from the Cancer Genome Atlas, molecular biologists Curt M. Horvath and Robert W. Said calculation techniques and powerful bioinformatic used to detect the expression profiles of genes in the two sub-types of cancer. They found that a small number of genes are activated by STAT3 signaling proteins in breast cancers basal-like, but not in luminal breast cancers.
basal-like cancer is a category that includes a number of different breast cancers, including very aggressive form called triple negative cancer.
"You can not treat breast cancer as a disease," said Horvath. "Cancer describes many molecular processes that go wrong. We teased from large amounts of data that 'STAT3 activity is correlated with distinct patterns of gene expression in a type of breast cancer, but not in another. "
The results are published today (August 19) in the online edition of the journal at the beginning of Proceedings of the National Academy of Sciences ( PNAS ).
results suggest a clinical study should be conducted of a drug inhibiting STAT3 in patients with basal-like cancers and luminal, Horvath said. Currently there are no pills or injections targeting STAT3 for patients with breast cancer.
Horvath is a professor of molecular biosciences Weinberg College Northwest of Arts and Sciences and professor of microbiology and immunology and of medicine at Northwestern University Feinberg School of Medicine.
previous research has found the STAT3 protein is overactive in many breast cancers, but its role has not been well understood. The search for Horvath and Tell is the first reported study to compare the subtypes of breast cancer and the expression profiles of genes associated with STAT3 in tumors of human patients.
Horvath pointed out that this is a statistical analysis and the results should be verified with laboratory experiments and clinical care. He plans to conduct such a study with colleagues from Lurie Comprehensive Cancer Center of Northwestern Robert H. University.
"The Cancer Genome Atlas is a rich database and more and more public data created to help us understand cancer," said Horvath, who is co-responsible for the transduction program signal in the cancer program at the Lurie cancer Center. "It enables basic scientists to ask interesting questions about cancer and contribute to clinical care."
Tell Horvath and observed that there are many clearly visible pattern of expression of common genes - which some genes are activated and some genes are switched off. - in basal-like cancers These clear patterns have not been observed in the luminal cancers
"This. opens the possibility that the specific signaling subtype of cancer is driven by STAT3 and that STAT3 inhibitors may be more effective in patients diagnosed with basal-like cancers than those with luminal cancer, "said Horvath .
STAT3 is synonymous with "signal transducer and activator of transcription 3," a transcription factor (protein) encoded by the gene STAT3 in humans. In addition to its known roles in cancer cells, STAT3 is a key mediator of cytokines and growth factors signals in normal cells that are important for various processes, including immunity and inflammation.
Tell, a postdoctoral fellow in the laboratory Horvath, had a keen interest in cancer and was very skilled in bioinformatics computing. In designing the study, he combined these two elements with the development of long Horvath Laboratory of STAT3, which has been implicated in cancer in general, both as a causative agent and a survival factor.
Horvath and Tell identified 84 genes that are differentially expressed in tumors basal cancer compared with luminal cancerous tumors. These genes are highly representative of the process of immune response and inflammation, Horvath said, and in agreement with the role of STAT3.
Tell and intensive analysis of Horvath used data from 825 patients with cancer of the breast around the country, each with hundreds of data points. The data included protein expression, protein phosphorylation, indicating that the signaling pathways are activated, and the messenger RNA and microRNA expression.
To sort large amounts of data, the researchers took advantage of Quest, a high performance computing system at Northwestern. The cluster of computers they used provided the equivalent processor and random access memory (RAM) of eight powerful desktop computers connected together.
The document title is "bioinformatics analysis reveals a STAT3-associated gene model-specific expression basal breast cancers in human tumors." Horvath and Tell are the authors of the document.
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