Biomarker for an Aggressive Breast Cancer Identified

Using bioinformatics, scientists have identified an overactive transcription factor strongly associated with basal-like breast carcinoma—providing a biomarker with potential for improved diagnostics and as a smart target for new therapeutics for patients with this highly aggressive, often chemotherapy-resistant cancer.

The biomarker STAT3 (signal transducer and activator of transcription 3) was identified by Northwestern University (Evanston, IL, USA) scientists Curt M. Horvath, professor of molecular biosciences and of microbiology-immunology, and Robert W. Tell, PhD, using breast cancer (BrCa) patient data from The Cancer Genome Atlas. Powerful computational and bioinformatics techniques were used to detect patterns of gene expression comparing two BrCa subtypes. They found a small number of genes that were activated by STAT3 signaling in basal-like BrCas but not in luminal BrCas. Data from 825 BrCa patients were analyzed, including protein expression, protein phosphorylation (generally indicating signal activation), and messenger RNA and microRNA expression data. Among various BrCas included in the basal-like cancer category is the highly aggressive form called triple negative cancer.

“We have 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,” said Prof. Horvath. The results suggest that a clinical study should be conducted of a STAT3-inhibiting drug. Currently there are no pills or injections targeting STAT3 for BrCa patients. This study “opens up the possibility that cancer subtype-specific signaling 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,” said Prof. Horvath.

Previous research has found the STAT3 protein to be overactive in many BrCas, but its role is not well understood. In addition to its known roles in cancerous cells, STAT3 in normal cells is an essential mediator of cytokine and growth factor signals important for diverse processes, including immunity and inflammation. Prof. Horvath and Dr. Tell identified 84 genes that are differentially expressed in basal-like cancer tumors compared to luminal cancer tumors. These genes are highly representative of immune response and inflammation processes consistent with the role of STAT3.

This is the first reported study to compare BrCa subtypes and gene expression patterns associated with STAT3 in the tumors of human patients. “The Cancer Genome Atlas is a really rich and growing database of publicly available data created to help us understand cancer,” said Prof. Horvath, “It allows basic scientists to ask interesting questions about cancer and contribute to clinical care.” He emphasized that this study is a statistical analysis and the findings need to be verified with careful laboratory and clinical experiments. He plans to conduct such a study with colleagues at Northwestern University’s Robert H. Lurie Comprehensive Cancer Center.

The findings were published August 19, 2014, in the online early edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

Related Links:
Northwestern University
The Cancer Genome Atlas