Exosomal Metabolic Signatures Are Associated with Differential Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer

• Authors: Shriya Joshi, Georgia State University; Chakravarthy Garlapati, Georgia State University; Shristi Bhattarai, Georgia State University; Yixin Su, Wake Forest School of Medicine; Leslimar Rios-Colon, Wake Forest School of Medicine; Gagan Deep, Wake Forest School of Medicine; Mylin Torres, Emory University; Ritu Aneja, Georgia State University
• Journal Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: Volume 23, Number 10
• Publisher: MDPI | 2022-05-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/ijms23105324
• Subjects: Health Sciences, Oncology; Biology, Radiation
• Keywords: Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry; breast cancer; neoadjuvant chemotherapy; pathologic complete response; residual disease; exosomes; metabolomics; MONOETHANOLAMINE; MECHANISM; CELLS

Abstract

Neoadjuvant chemotherapy (NAC) is commonly used in breast cancer (BC) patients to increase eligibility for breast-conserving surgery. Only 30% of patients with BC show pathologic complete response (pCR) after NAC, and residual disease (RD) is associated with poor long-term prognosis. A critical barrier to improving NAC outcomes in patients with BC is the limited understanding of the mechanisms underlying differential treatment outcomes. In this study, we evaluated the ability of exosomal metabolic profiles to predict NAC response in patients with BC. Exosomes isolated from the plasma of patients after NAC were used for metabolomic analyses to identify exosomal metabolic signatures associated with the NAC response. Among the 16 BC patients who received NAC, eight had a pCR, and eight had RD. Patients with RD had 2.52-fold higher exosome concentration in their plasma than those with pCR and showed significant enrichment of various metabolic pathways, including citrate cycle, urea cycle, porphyrin metabolism, glycolysis, and gluconeogenesis. Additionally, the relative exosomal levels of succinate and lactate were significantly higher in patients with RD than in those with pCR. These data suggest that plasma exosomal metabolic signatures could be associated with differential NAC outcomes in BC patients and provide insight into the metabolic determinants of NAC response in patients with BC.