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Onc."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 &gt;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.<\/jats:p>","DOI":"10.1038\/s41698-024-00520-1","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T19:02:06Z","timestamp":1707246126000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Single-cell low-pass whole genome sequencing accurately detects circulating tumor cells for liquid biopsy-based multi-cancer diagnosis"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7006-6617","authenticated-orcid":false,"given":"Xiaohan","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3647-8140","authenticated-orcid":false,"given":"Ziming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1060-0512","authenticated-orcid":false,"given":"Haimiao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8403-9452","authenticated-orcid":false,"given":"Qihui","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"520_CR1","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan, D. & Weinberg, R. 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