Diabetes-associated breast cancer has a distinct transcriptome and metabolome and shows DNA repair deficiency [Breast Tumors]

Diabetes commonly affects cancer patients. As a comorbidity, it may modify tumor biology and therapy response. Yet, we still lack an understanding of the diabetes-induced molecular changes in human breast tumors and their implication for therapy. The goal of this study was aimed to identify diabetes induced phenotypes and molecular signatures in breast cancer. Here, we investigated the effect of diabetes on breast cancer biology using a three-pronged approach that included analysis of orthotopic human tumor xenografts, patient tumors, and breast cancer cells exposed to diabetes and hyperglycemia. Diabetes and hyperglycemia induced a mesenchymal and stem cell-like phenotypes. Further Diabetes and hyperglycemia also associated with oxidative stress and both gene expression and mutational signatures of DNA repair deficiency. Breast cancer cells cultured under hyperglycemia acquired increased DNA damage and sensitivity to DNA damage response inhibitors. Based on these observations, diabetes-associated breast tumors may show an increased drug response to DNA repair pathway inhibitors that are cancer therapeutics. RNA was isolated from frozen breast tumors with/without diabetes (n = 36 diabetic and n = 37 non-diabetic) using TRIzol method. The mRNA profiles of the above breast tumors were generated by deep sequencing using Illumina NextSeq.