Metabolomics by NMR Combined with Machine Learning to Predict Neoadjuvant Chemotherapy Response for Breast Cancer

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Cardoso, Marcella R. ; Silva, Alex Ap Rosini ; Talarico, Maria Cecilia R. ; Sanches, Pedro H. Godoy ; Sforca, Mauricio L. ; Rocco, Silvana A. ; Rezende, Luciana M. ; Quintero, Melissa ; Costa, Tassia B. B. C. ; Viana, Lais R. ; Canevarolo, Rafael R. ; Ferracini, Amanda C. ; Ramalho, Susana ; Gutierrez, Junier Marrero ; Guimaraes, Fernando ; Tasic, Ljubica ; Tata, Alessandra ; Sarian, Luis O. ; Cheng, Leo L. ; Porcari, Andreia M. ; Derchain, Sophie F. M.

• Tipo de documento: Artigo Científico
• Fonte: CANCERS; v. 14, n. 20, p. 16-pg., 2022-10-01.

Resumo

Simple Summary Neoadjuvant chemotherapy (NACT) is offered to breast cancer (BC) patients to downstage the disease. However, some patients may not respond to NACT, being resistant. We used the serum metabolic profile by Nuclear Magnetic Resonance (NMR) combined with disease characteristics to differentiate between sensitive and resistant BC patients. We obtained accuracy above 80% for the response prediction and showcased how NMR can substantially enhance the prediction of response to NACT. Neoadjuvant chemotherapy (NACT) is offered to patients with operable or inoperable breast cancer (BC) to downstage the disease. Clinical responses to NACT may vary depending on a few known clinical and biological features, but the diversity of responses to NACT is not fully understood. In this study, 80 women had their metabolite profiles of pre-treatment sera analyzed for potential NACT response biomarker candidates in combination with immunohistochemical parameters using Nuclear Magnetic Resonance (NMR). Sixty-four percent of the patients were resistant to chemotherapy. NMR, hormonal receptors (HR), human epidermal growth factor receptor 2 (HER2), and the nuclear protein Ki67 were combined through machine learning (ML) to predict the response to NACT. Metabolites such as leucine, formate, valine, and proline, along with hormone receptor status, were discriminants of response to NACT. The glyoxylate and dicarboxylate metabolism was found to be involved in the resistance to NACT. We obtained an accuracy in excess of 80% for the prediction of response to NACT combining metabolomic and tumor profile data. Our results suggest that NMR data can substantially enhance the prediction of response to NACT when used in combination with already known response prediction factors. (AU)

• Processo FAPESP: 18/24069-3 - Do biomonitoramento ao reconhecimento de assinaturas do exposoma humano visando antecipar riscos para uma saúde contínua
• Beneficiário: Fernando Barbosa Júnior
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/04314-6 - Imageamento e metabolômica por espectrometria de massas aplicada ao estudo de resistência à terapia neoadjuvante para tratamento de câncer de mama: busca por um teste preditivo
• Beneficiário: Andréia de Melo Porcari
• Modalidade de apoio: Auxílio à Pesquisa - Regular