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<p>The heterogeneity in the different primary tumor sites of metabolic-immune networks across multifocal tumors remains a critical barrier to precision therapy in breast cancer. Single-platform mass spectrometry (MS) approaches provide valuable molecular insights but lack the comprehensive coverage necessary for a systems-level understanding. Here, we propose a multi-omics strategy that integrates MS-based metabolomics and lipidomics with mass cytometry (CyTOF)-based single-cell immune analysis. This strategy aims to map the dynamic interplay between metabolic reprogramming and immune remodeling in the MMTV-PyMT transgenic model of spontaneous mammary tumorigenesis. Our findings reveal a primary focus-dependent metabolic-immune heterogeneity at the inter/intra-tumor situation, including the disturbance of reprogramming of glycerophospholipid metabolism (164 differential lipids, <i>p</i> &lt; 0.05, FC &gt; 2), infiltration degree of myeloid cells in cervical and thoracic, abdominal, and inguinal locations. Single-cell immunome profiling demonstrates that myeloid infiltration exhibits anatomical preferences, with the cervical and thoracic regions showing 8.4 times more CD11b<sup>+</sup> cells than the abdominal and inguinal regions (<i>p</i> &lt; 0.01). Multimodal integration through Spearman bivariate correlation analysis identifies the strong co-regulation between glycerophospholipids expression and the quantitative proportion of pro-tumorigenic myeloid subsets (|<i>R</i>| &gt; 0.88, 0.05 &lt; <i>p</i> &lt; 0.001). This study establishes a paradigm for investigating tumor ecosystem complexity through coordinated multi-omics analysis, revealing primary-site-encoded metabolic-immune circuits that could guide location-specific therapeutic interventions.</p>

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Mass Spectrometry-Based Multi-Omics Integration Decodes Metabolic-Immune Crosstalk in Multifocal Breast Cancer Progression

  • 期刊论文

  • 发表日期：

    2026年4月17日

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  • Tianyou Cao,
  • Yu Xiao,
  • Zhiyi Yang,
  • Peng Zhou,
  • Xuantong Liu,
  • Xinwei Lv,
  • Yashan Liu,
  • Xiaotian Tan,
  • Chao Zhao,
  • Qian Luo

摘要

The heterogeneity in the different primary tumor sites of metabolic-immune networks across multifocal tumors remains a critical barrier to precision therapy in breast cancer. Single-platform mass spectrometry (MS) approaches provide valuable molecular insights but lack the comprehensive coverage necessary for a systems-level understanding. Here, we propose a multi-omics strategy that integrates MS-based metabolomics and lipidomics with mass cytometry (CyTOF)-based single-cell immune analysis. This strategy aims to map the dynamic interplay between metabolic reprogramming and immune remodeling in the MMTV-PyMT transgenic model of spontaneous mammary tumorigenesis. Our findings reveal a primary focus-dependent metabolic-immune heterogeneity at the inter/intra-tumor situation, including the disturbance of reprogramming of glycerophospholipid metabolism (164 differential lipids, p < 0.05, FC > 2), infiltration degree of myeloid cells in cervical and thoracic, abdominal, and inguinal locations. Single-cell immunome profiling demonstrates that myeloid infiltration exhibits anatomical preferences, with the cervical and thoracic regions showing 8.4 times more CD11b+ cells than the abdominal and inguinal regions (p < 0.01). Multimodal integration through Spearman bivariate correlation analysis identifies the strong co-regulation between glycerophospholipids expression and the quantitative proportion of pro-tumorigenic myeloid subsets (|R| > 0.88, 0.05 < p < 0.001). This study establishes a paradigm for investigating tumor ecosystem complexity through coordinated multi-omics analysis, revealing primary-site-encoded metabolic-immune circuits that could guide location-specific therapeutic interventions.