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<p>Multimodal profiling of circulating tumor cells (CTCs) and non-tumor circulating cells was performed in six patients with advanced colorectal cancer to identify biological programs beyond enumeration-based analyses. Across all patients, we identified 3,981 CTCs characterized by pronounced EpCAM/L1CAM co-expression, variable PD-L1 expression, and low LGR5 expression, consistent with metastatic-associated phenotypes. Integrated single-cell multi-omics analysis of 1,720 cells revealed genomic instability within EpCAM⁺, L1CAM⁺, LGR5⁺, and PD-L1⁺ CTC subsets, including Y-chromosome loss in male patients and marked intra-patient heterogeneity. In parallel, non-CTCs exhibited upregulation of inflammatory and metabolic dysregulation programs. This hypothesis-generating study highlights the relevance of blood-based multimodal single-cell profiling for interrogating tumor–host states beyond insights from CTC enumeration alone.</p>

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A multimodal single-cell framework for ecosystem-level profiling of circulating tumor and non-tumor cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月19日

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  • Gabriela Felix,
  • Francesca Aguirre,
  • Lisa Zhou,
  • Aaron Denmark,
  • Rocio Alvarez,
  • Daniel M. Kim,
  • Jun Gong,
  • Megan P. Hitchins

摘要

Multimodal profiling of circulating tumor cells (CTCs) and non-tumor circulating cells was performed in six patients with advanced colorectal cancer to identify biological programs beyond enumeration-based analyses. Across all patients, we identified 3,981 CTCs characterized by pronounced EpCAM/L1CAM co-expression, variable PD-L1 expression, and low LGR5 expression, consistent with metastatic-associated phenotypes. Integrated single-cell multi-omics analysis of 1,720 cells revealed genomic instability within EpCAM⁺, L1CAM⁺, LGR5⁺, and PD-L1⁺ CTC subsets, including Y-chromosome loss in male patients and marked intra-patient heterogeneity. In parallel, non-CTCs exhibited upregulation of inflammatory and metabolic dysregulation programs. This hypothesis-generating study highlights the relevance of blood-based multimodal single-cell profiling for interrogating tumor–host states beyond insights from CTC enumeration alone.