Differential expression of fatty acid desaturase 1 in triple negative breast cancer.
Women diagnosed with triple negative breast cancer can benefit neither from endocrine therapy nor from HER2-targeted therapies (1). We mined published microarray datasets (2, 3) to determine in an unbiased fashion and at the systems level genes most differentially expressed in the primary tumors of patients with breast cancer. We report here significant differential expression of the gene encoding fatty acid desaturase 1, FADS1, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). FADS1 was also differentially expressed in bulk tumor in human breast cancer (3). FADS1 mRNA was present at significantly increased quantities in TNBC tumor cells relative to normal mammary ductal cells. Analysis of human survival data revealed that expression of FADS1 in primary tumors of the breast was correlated with recurrence-free survival in patients with basal-like and normal-like subtype cancer, while within triple negative breast cancer, primary tumor expression of FADS1 was correlated with distant metastasis-free survival in patients with basal-like 1 and immunomodulatory subtype disease. FADS1 may be of relevance to initiation, maintenance or progression of triple negative breast cancers. We previously reported (4) that the fatty acid desaturase 2, FADS2, was also among the genes most differentially expressed in triple negative and in early-onset breast cancers (2, 3) in humans. Together, the data suggest that these enzymes (5), their transcriptome-wide differential expression, marked transcriptional up-regulation and accessible catalytic sites may make them suitable for therapeutic targeting.