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Breast Cancer Research
Published in: Breast Cancer Research 1/2024

Open Access 01-12-2024 | Breast Cancer | Research

Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer

Authors: Ningning Zhang, Yuxin Huang, Guanwen Wang, Yimei Xiang, Zhouhong Jing, Junjie Zeng, Feng Yu, Xianjun Pan, Wenqi Zhou, Xiaohua Zeng

Published in: Breast Cancer Research | Issue 1/2024

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Abstract

Background

This study aimed to explore potential indicators associated with the neoadjuvant efficacy of TCbHP regimen (taxane, carboplatin, trastuzumab, and pertuzumab) in HER2 + breast cancer (BrCa) patients.

Methods

A total of 120 plasma samples from 40 patients with HER2 + BrCa were prospectively collected at three treatment times of neoadjuvant therapy (NAT) with TCbHP regimen. Serum metabolites were analyzed based on LC-MS and GC-MS data. Random forest was used to establish predictive models based on pre-therapeutic differentially expressed metabolites. Time series analysis was used to obtain potential monitors for treatment response. Transcriptome analysis was performed in nine available pre‑therapeutic specimens of core needle biopsies. Integrated analyses of metabolomics and transcriptomics were also performed in these nine patients. qRT-PCR was used to detect altered genes in trastuzumab-sensitive and trastuzumab-resistant cell lines.

Results

Twenty-one patients achieved pCR, and 19 patients achieved non-pCR. There were significant differences in plasma metabolic profiles before and during treatment. A total of 100 differential metabolites were identified between pCR patients and non-pCR patients at baseline; these metabolites were markedly enriched in 40 metabolic pathways. The area under the curve (AUC) values for discriminating the pCR and non-PCR groups from the NAT of the single potential metabolite [sophorose, N-(2-acetamido) iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] or combined panel of these metabolites were greater than 0.910. Eighteen metabolites exhibited potential for monitoring efficacy. Several validated genes might be associated with trastuzumab resistance. Thirty-nine altered pathways were found to be abnormally expressed at both the transcriptional and metabolic levels.

Conclusion

Serum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.
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Metadata
Title
Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer
Authors
Ningning Zhang
Yuxin Huang
Guanwen Wang
Yimei Xiang
Zhouhong Jing
Junjie Zeng
Feng Yu
Xianjun Pan
Wenqi Zhou
Xiaohua Zeng
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2024
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-024-01813-w

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