Integration of multi-omics data shows downregulation of mismatch repair, purin, and tublin pathways in AR-negative triple-negative chemotherapy-resistant breast tumors

ABSTRACT Triple negative breast cancer (TNBC) patients who fail to achieve a pathological complete response to neoadjuvant chemotherapy (NAC) will likely experience recurrence of the disease within 3-4 years. Prognostic assessment of early recurrence could facilitate clinical decisions and impact disease survival. This study investigated pre- and post-NAC multi-omics data from both an in-house and a public clinical study to identify biomarkers of NAC response. We observed significant transcriptional differences associated with response in the residual disease (post-NAC biopsies), which did not exist in the pre-NAC biopsies. We further refined the post-NAC transcriptional changes to a 17-gene signature and machine learning models were applied to evaluate the signature’s diagnostic potential (area under the curve ≥ 0.8). Interestingly, the signature was enriched with down-regulated immune genes and several of these genes demonstrated prognostic potential in basal TNBC tumors. Our 17-gene signature provides additional insight into TNBC recurrence, which warrants further investigation.