软脑膜疾病患者脑脊液中检测到的单细胞和无细胞成分的多组学特征分析

Multi-Omic Characterization of Single Cells and Cell-Free Components Detected in the Cerebrospinal Fluid of Patients with Leptomeningeal Disease.

作者信息

Shishido Stephanie N, Marvit Amelia, Pham Doanna, Luo Theresa, Xu Liya, Mason Jeremy, Priceman Saul J, Portnow Jana, Kuhn Peter

机构信息

Convergent Science Institute for Cancer, Michelson Center, University of Southern California, Los Angeles, CA 90089, USA.

The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.

出版信息

Cancers (Basel). 2024 Nov 6;16(22):3746. doi: 10.3390/cancers16223746.

DOI:10.3390/cancers16223746

PMID:39594700

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11592257/

Abstract

BACKGROUND/OBJECTIVES: Up to 30% of patients with breast cancers will develop brain or leptomeningeal metastases, and this risk is especially high with HER2-positive cancers. For patients with central nervous system metastases, cerebrospinal fluid (CSF) liquid biopsies are a promising opportunity to monitor disease, inform treatment, and predict prognosis. This pilot study investigated CSF liquid biopsy analytes from three patients diagnosed with central nervous system metastases based on imaging but not confirmed via clinical cytology.

METHODS

The detection of cellular analytes with the non-enrichment high-definition single-cell assay (HDSCA3.0) workflow was compared between the CSF and matched peripheral blood (PB) samples.

RESULTS

Circulating tumor cells (CTCs) were detected in the CSF but not the PB and were subsequently molecularly characterized using single-cell genomics and targeted multiplexed proteomics to reveal a clonal population of phenotypically heterogeneous cells. There was a lack of concordance in the copy number alteration profiles between CTCs and cell-free DNA (cfDNA) in the CSF. Extracellular vesicle surface marker analysis in CSF revealed a prominent signal among tetraspanins (CD9/CD63/CD81), with CD81 exhibiting the highest signal across all patients.

CONCLUSIONS

The data presented suggest that CSF could be a useful tool for diagnosing and assessing disease severity.

摘要

背景/目的：高达30%的乳腺癌患者会发生脑转移或软脑膜转移，HER2阳性癌症患者发生这种转移的风险尤其高。对于中枢神经系统转移患者，脑脊液（CSF）液体活检是监测疾病、指导治疗和预测预后的一个有前景的方法。这项初步研究调查了3例经影像学诊断为中枢神经系统转移但未经临床细胞学确诊的患者的脑脊液液体活检分析物。

方法

采用非富集高清单细胞分析（HDSCA3.0）工作流程，比较脑脊液和匹配的外周血（PB）样本中细胞分析物的检测情况。

结果

在脑脊液中检测到循环肿瘤细胞（CTC），在外周血中未检测到，随后使用单细胞基因组学和靶向多重蛋白质组学对其进行分子特征分析，以揭示一群表型异质性的克隆细胞。脑脊液中CTC与游离DNA（cfDNA）的拷贝数改变谱不一致。脑脊液中外泌体表面标志物分析显示，四跨膜蛋白（CD9/CD63/CD81）中有一个突出信号，所有患者中CD81信号最高。