Differential expression of ribonucleotide reductase regulatory subunit M2 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 ribonucleotide reductase regulatory subunit M2, RRM2, when comparing the tumor cells of patients with triple negative breast cancer to normal mammary ductal cells (2). RRM2 was also differentially expressed in bulk tumor in human breast cancer (3). RRM2 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 RRM2 in primary tumors of the breast was correlated with recurrence-free survival in patients with luminal A type cancer, while within triple negative breast cancer, primary tumor expression of RRM2 was correlated with distant metastasis-free survival in patients with luminal androgen receptor subtype disease. RRM2 may be of relevance to initiation, maintenance or progression of triple negative breast cancers.