Single-cell low-pass whole genome sequencing accurately detects circulating tumor cells for liquid biopsy-based multi-cancer diagnosis

Accurate detection of circulating tumor cells (CTCs) in blood and non-blood body fluids enables generation of deterministic cancer diagnosis and represent a less invasive and safer liquid biopsy approach. Although genomic alternations have been widely used in circulating tumor DNA (ctDNA) analysis,...

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Bibliographic Details
Published in:NPJ precision oncology 2024-02, Vol.8 (1), p.30-30, Article 30
Main Authors: Shen, Xiaohan, Dai, Jiao, Guo, Lingchuan, Liu, Zhigang, Yang, Liu, Gu, Dongmei, Xie, Yinghong, Wang, Zhuo, Li, Ziming, Xu, Haimiao, Shi, Qihui
Format: Article
Language:English
Subjects:
631/1647/514/2254
692/4017
Ascites
Biopsy
Body fluids
Cancer
Cancer Research
Gene Therapy
Genomes
Human Genetics
Internal Medicine
Medical diagnosis
Medicine
Medicine & Public Health
Metastasis
Oncology
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Summary:Accurate detection of circulating tumor cells (CTCs) in blood and non-blood body fluids enables generation of deterministic cancer diagnosis and represent a less invasive and safer liquid biopsy approach. Although genomic alternations have been widely used in circulating tumor DNA (ctDNA) analysis, studies on cell-based genomic alternations profiling for CTC detection are rare due to major technical limitations in single-cell whole genome sequencing (WGS) including low throughput, low accuracy and high cost. We report a single-cell low-pass WGS-based protocol (scMet-Seq) for sensitive and accurate CTC detection by combining a metabolic function-associated marker Hexokinase 2 (HK2) and a Tn5 transposome-based WGS method with improved cell fixation strategy. To explore the clinical use, scMet-Seq has been investigated with blood and non-blood body fluids in diagnosing metastatic diseases, including ascites-based diagnosis of malignant ascites (MA) and blood-based diagnosis of metastatic small-cell lung cancer (SCLC). ScMet-Seq shows high diagnostic sensitivity (MA: 79% in >10 cancer types; metastatic SCLC: 90%) and ~100% of diagnostic specificity and positive predictive value, superior to clinical cytology that exhibits diagnostic sensitivity of 52% in MA diagnosis and could not generate blood-based diagnosis. ScMet-Seq represents a liquid biopsy approach for deterministic cancer diagnosis in different types of cancers and body fluids.
ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-024-00520-1