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<p>Lung adenocarcinoma (LUAD)-derived leptomeningeal metastases (LM) represent a predominant subtype among all LM cases. Nevertheless, the cerebrospinal fluid (CSF) profile of LUAD-LM patients remains poorly characterized and reliable CSF diagnostic biomarkers for LUAD-LM have yet to be established. Using single-cell RNA sequencing data of CSF cells from six LUAD-LM patients, we drew a systematic transcriptomic atlas of the CSF cellular landscape. Our analysis revealed that LUAD-LM reprograms CSF into an immunosuppressive state, marked by the emergence of pro-tumoral LGMN-SELENOP<sup>high</sup> macrophages and proliferating CSF circulating tumor cells (CSF-CTC). Cell-cell communication analysis showed that CSF-CTC reinforces immunosuppression by co-inhibitory checkpoint axis NECTIN2_TIGIT axis with the CD8<sup>+</sup>T/NK cells, and via CD47_SIRPA axis with antigen-presenting cells. Furthermore, we identified the single-cell transcriptomic difference between CSF-CTC and tumor cells of parenchymal brain metastases (PBM). Notably, Trophoblast cell surface antigen 2 (TROP2) levels in CSF were significantly elevated in LUAD-LM patients versus both normal controls (NC) and LUAD patients without LM (Non-LM). It showed strong diagnostic accuracy for distinguishing LUAD LM from Non-LM or NC, and PBM did not influence the CSF TROP2 level. Collectively, our findings advance the understanding of LUAD-LM pathogenesis and highlight the potential of CSF TROP2 as a diagnostic biomarker for LM.</p>

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Cellular landscape and diagnostic value of TROP2 in cerebrospinal fluid of lung adenocarcinoma leptomeningeal metastases

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月24日

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  • Zhe Wang,
  • Jie Luo,
  • Yuexinzi Jin,
  • Ting Wang,
  • Yuan Mu,
  • Jinping Liu,
  • Huanyu Ju,
  • Yuqing Wu,
  • Qingjian Ou,
  • Ming Guan,
  • Haoyu Ruan

摘要

Lung adenocarcinoma (LUAD)-derived leptomeningeal metastases (LM) represent a predominant subtype among all LM cases. Nevertheless, the cerebrospinal fluid (CSF) profile of LUAD-LM patients remains poorly characterized and reliable CSF diagnostic biomarkers for LUAD-LM have yet to be established. Using single-cell RNA sequencing data of CSF cells from six LUAD-LM patients, we drew a systematic transcriptomic atlas of the CSF cellular landscape. Our analysis revealed that LUAD-LM reprograms CSF into an immunosuppressive state, marked by the emergence of pro-tumoral LGMN-SELENOPhigh macrophages and proliferating CSF circulating tumor cells (CSF-CTC). Cell-cell communication analysis showed that CSF-CTC reinforces immunosuppression by co-inhibitory checkpoint axis NECTIN2_TIGIT axis with the CD8+T/NK cells, and via CD47_SIRPA axis with antigen-presenting cells. Furthermore, we identified the single-cell transcriptomic difference between CSF-CTC and tumor cells of parenchymal brain metastases (PBM). Notably, Trophoblast cell surface antigen 2 (TROP2) levels in CSF were significantly elevated in LUAD-LM patients versus both normal controls (NC) and LUAD patients without LM (Non-LM). It showed strong diagnostic accuracy for distinguishing LUAD LM from Non-LM or NC, and PBM did not influence the CSF TROP2 level. Collectively, our findings advance the understanding of LUAD-LM pathogenesis and highlight the potential of CSF TROP2 as a diagnostic biomarker for LM.