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23-04-2024 | Breast Cancer | Original Article

Global untargeted and individual targeted plasma metabolomics of breast cancer recurrence modified by hormone receptors

Authors: Pei-Jing Yang, Eing-Mei Tsai, Ming-Feng Hou, Yen-Jung Lee, Tsu-Nai Wang

Abstract

Background

Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis.

Methods

We recruited breast cancer patients from Kaohsiung Medical University (KMU) to perform untargeted (case–control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model.

Results

In the discovery phase, partial least squares-discriminant analysis (PLS-DA) showed that plasma metabolites were significantly different between recurrent and non-recurrent breast cancer patients. Metabolite set enrichment analysis (MSEA) and metabolomic pathway analysis (MetPA) showed that valine, leucine, and isoleucine degradation was the significant pathway, and volcano plot showed significant ten upregulated and two downregulated metabolites between recurrent and non-recurrent cases. Combined with receiver operating characteristic (ROC) curve and biological significance, creatine, valine, methionine, and mannose were selected for the validation phase. In this patient cohort with 41 new-recurrent vs. 248 non-recurrent breast cancer cases, followed for 720.49 person-years, compared with low level of valine, high valine level was significantly negatively associated with recurrent breast cancer (aHR: 0.36, 95% CI: 0.18–0.72, P = 0.004), especially in ER-negative and PR-negative status. There were interaction effects between valine and ER (P_interaction = 0.006) as well as PR (P_interaction = 0.002) on recurrent breast cancer. After Bonferroni correction, stratification effects between valine and hormone receptors were still significant.

Conclusion

Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.

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Title: Global untargeted and individual targeted plasma metabolomics of breast cancer recurrence modified by hormone receptors
Authors: Pei-Jing Yang
Eing-Mei Tsai
Ming-Feng Hou
Yen-Jung Lee
Tsu-Nai Wang
Publication date: 23-04-2024
Publisher: Springer Nature Singapore
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI: https://doi.org/10.1007/s12282-024-01579-1

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