Circulating tumor cell characterization of lung cancer brain metastasis in the cerebrospinal fluid through single-cell transcriptome analysis

MedRxiv : the Preprint Server for Health Sciences
H. RuanM. Guan


Brain metastases explain the majority of lung cancer associated mortality, which is the leading cause of cancer death. Cytological analysis in the cerebrospinal fluid (CSF) remains the diagnostic gold standard, and the circulating tumor cells (CTCs) in CSF is not well defined at molecular and transcriptome level. We established an effective CSF-CTC collection procedure and isolated individual CSF cells from lung adenocarcinoma leptomeningeal metastases (LUAD-LM) patients and controls. 3,744 single-cell transcriptomes were sequenced and analyzed to perform a comprehensive characterization of CSF cells. Through clustering and expression analysis, we defined CSF-CTCs at the transcriptome level based on epithelial markers, proliferative markers and genes with lung origin. 290 genes are upregulated by 2-fold in LUAD-LM patients. These metastatic-CTC signature genes are enriched for metabolic pathway and cell-adhesion molecule categories, indicating their roles in tumor cell survival and metastases. We discovered substantial heterogeneity in patient CSF-CTCs, in sharp contrast to the lack of heterogeneity in cancer cell lines or xenograft models. We quantified the degree of heterogeneity and found significantly greater among-patient ...Continue Reading

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