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

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

doi:10.1007/s12282-024-01579-1

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

Breast Cancer. 2024 Apr 23. doi: 10.1007/s12282-024-01579-1. Online ahead of print.

Authors

Pei-Jing Yang¹, Eing-Mei Tsai^{2

3}, Ming-Feng Hou^{4

5}, Yen-Jung Lee⁶, Tsu-Nai Wang^{7

8}

Affiliations

¹ Department of Public Health, College of Health Science, Kaohsiung Medical University, No. 100, Shin-Chuan 1St Road, Sanmin Dist., Kaohsiung, 80708, Taiwan.
² Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, No.100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung, 80708, Taiwan.
³ Department of Obstetrics and Gynecology, Kaohsiung Medical University Chung-Ho Memorial Hospital, No.100, Tzyou 1st Road, Sanmin Dist., Kaohsiung, 80756, Taiwan.
⁴ Division of Breast Oncology and Surgery, Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, No.100, Tzyou 1st Road, Sanmin Dist., Kaohsiung, 80756, Taiwan.
⁵ Department of Biomedical Science and Environmental Biology, College of Life Science, Kaohsiung Medical University, No.100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung, 80708, Taiwan.
⁶ Center for Research Resources and Development, Kaohsiung Medical University, No.100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung, 80708, Taiwan.
⁷ Department of Public Health, College of Health Science, Kaohsiung Medical University, No. 100, Shin-Chuan 1St Road, Sanmin Dist., Kaohsiung, 80708, Taiwan. wangtn@kmu.edu.tw.
⁸ Research Center for Environmental Medicine, Kaohsiung Medical University, No.100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung, 80708, Taiwan. wangtn@kmu.edu.tw.

PMID: 38652345
DOI: 10.1007/s12282-024-01579-1

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.

Keywords: Hormone receptors; Interaction effects; Metabolomics; Patient cohort; Recurrent breast cancer.

Abstract

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