PO.BCS01.11 · 生物信息与计算
单细胞转录组和CNV分析揭示胰腺导管腺癌中独特的循环肿瘤细胞特征
Single-cell transcriptomic and CNV profiling reveal distinct circulating tumor cell signatures in pancreatic ductal adenocarcinoma
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
胰腺导管腺癌（PDAC）是一种预后不良、早期检测手段有限的侵袭性恶性肿瘤。循环肿瘤细胞（CTC）为研究肿瘤异质性和疾病进展提供了微创的机会，但在外周血细胞中可靠地识别它们仍具挑战性。在本研究中，从PDAC患者和健康对照采集外周血样本。使用CytoGen的Smart Biopsy™平台富集CTC，并采用单细胞RNA测序（Cell Ranger 8.0.1）分析CTC富集组分。过滤掉低质量细胞和双联体细胞（nFeature_RNA>500，percent.mt<10，双联体评分<0.25）。降维和聚类（分辨率0.8）实现了细胞类型注释，并在亚簇水平（k=5）推断拷贝数变异（CNV）谱以评估潜在的恶性特征。因此，识别出展现PDAC相关转录特征的独特细胞簇。CNV模式分析显示，某些细胞簇表现出与典型免疫和血细胞群体不同的基因组变异性。与TCGA-PAAD参照数据的比较表明，其与肿瘤样CNV谱部分相似。此外，基于CNV的分层倾向于将PDAC来源的CTC富集簇与健康血液中观察到的簇区分开来，提示其潜在的诊断价值。总体而言，这些整合的单细胞转录组和CNV分析为PDAC中的CTC异质性提供了宝贵见解，并提示基于CNV的分析可能有助于识别推定的CTC群体，并促进未来用于基于液体活检的癌症监测的生物标志物开发。
致谢：本工作由韩国科学技术信息通信部资助的韩国国家研究基金会（NRF）支持（RS-2023-00261820）。
查看英文原文 English abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and limited early detection methods. Circulating tumor cells (CTCs) provide a minimally invasive opportunity to investigate tumor heterogeneity and disease progression, yet their reliable identification among peripheral blood cells remains challenging. In this study, peripheral blood samples were collected from PDAC patients and healthy controls. CTCs were enriched using CytoGen's Smart Biopsy™ Platform, and the CTC-enriched fractions were analyzed using single-cell RNA sequencing (Cell Ranger 8.0.1). Low-quality and doublet cells were filtered (nFeature_RNA > 500, percent.mt < 10, doublet score < 0.25). Dimensional reduction and clustering (resolution 0.8) enabled cell type annotation, and copy number variation (CNV) profiles were inferred at the subcluster level (k=5) to assess potential malignant characteristics. Consequently, Distinct cell clusters exhibiting PDAC-associated transcriptional signatures were identified. CNV pattern analyses revealed that certain clusters displayed genomic variability distinct from typical immune and blood cell populations. Comparison with TCGA-PAAD reference data indicated partial resemblance to tumor-like CNV profiles. Moreover, CNV-based stratification tended to distinguish PDAC-derived CTC-enriched clusters from those observed in healthy blood, suggesting potential diagnostic utility. Overall, these integrative single-cell transcriptomic and CNV analyses provide valuable insights into CTC heterogeneity in PDAC and suggest that CNV-informed profiling may enhance the identification of putative CTC populations and facilitate future biomarker development for liquid biopsy-based cancer monitoring.
Acknowledgement: This work is supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (RS-2023-00261820).
利益披露 Disclosure
S. Choi, None..
J. Lee, None..
H. Kee, None..
M. Chung, None..
J. Kim, None..
S. Lee, None.