Bioinformatic analysis reveals a pattern of STAT3-associated gene expression specific to basal-like breast cancers in human tumors

Abstract

Signal transducer and activator of transcription 3 (STAT3), a latent transcription factor associated with inflammatory signaling and innate and adaptive immune responses, is known to be aberrantly activated in a wide variety of cancers. In vitro analysis of STAT3 in human cancer cell lines has elucidated a number of specific targets associated with poor prognosis in breast cancer. However, to date, no comparison of cancer subtype and gene expression associated with STAT3 signaling in human patients has been reported. In silico analysis of human breast cancer microarray and reverse-phase protein array data was performed to identify expression patterns associated with STAT3 in basal-like and luminal breast cancers. Results indicate clearly identifiable STAT3-regulated signatures common to basal-like breast cancers but not to luminal A or luminal B cancers. Furthermore, these differentially expressed genes are associated with immune signaling and inflammation, a known phenotype of basal-like cancers. These findings demonstrate a distinct role for STAT3 signaling in basal breast cancers, and underscore the importance of considering subtype-specific molecular pathways that contribute to tissue-specific cancers.