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

作者：Ningning Zhang, Yuxin Huang, Guanwen Wang, Yimei Xiang, Zhouhong Jing, Junjie Zeng, Yu Feng, Xianjun Pan, Wenqi Zhou, Xiaohua Zeng · 发表于：Breast Cancer Research · 年份：2024 · DOI：10.1186/s13058-024-01813-w · 被引用次数：16 · 研究领域：Cancer Treatment and Pharmacology、Breast Cancer Treatment Studies、Cancer, Hypoxia, and Metabolism

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 ...