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

• DOI: 10.1038/s41698-024-00520-1
• Publication Date: 2024-02-06T19:02:06Z
• Authors: Xiaohan Shen; Jiao Dai; Lingchuan Guo; Zhigang Liu; Liu Yang; Dongmei Gu; Yinghong Xie; Zhuo Wang; Ziming Li; Haimiao Xu; Qihui Shi
• Keywords: Liquid biopsy; Circulating tumor cell; Cell-free fetal DNA

Abstract Accurate detection of circulating tumor cells (CTCs) in blood and non-blood body fluids enables generation deterministic cancer diagnosis represent a less invasive safer liquid biopsy approach. Although genomic alternations have been widely used DNA (ctDNA) analysis, studies on cell-based profiling for CTC are rare due to major technical limitations single-cell whole genome sequencing (WGS) including low throughput, accuracy high cost. We report low-pass WGS-based protocol (scMet-Seq) sensitive accurate by combining metabolic function-associated marker Hexokinase 2 (HK2) Tn5 transposome-based WGS method with improved cell fixation strategy. To explore the clinical use, scMet-Seq has investigated diagnosing metastatic diseases, ascites-based malignant ascites (MA) blood-based small-cell lung (SCLC). ScMet-Seq shows diagnostic sensitivity (MA: 79% >10 types; SCLC: 90%) ~100% specificity positive predictive value, superior cytology that exhibits 52% MA could not generate diagnosis. represents approach different types cancers fluids.