Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
28
10
2021
accepted:
25
07
2022
pubmed:
9
9
2022
medline:
18
2
2023
entrez:
8
9
2022
Statut:
ppublish
Résumé
The analysis of cell-free DNA (cfDNA) in plasma provides information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state. We developed a single-molecule multiparametric assay to comprehensively profile the epigenetics of plasma-isolated nucleosomes (EPINUC), DNA methylation and cancer-specific protein biomarkers. Our system allows for high-resolution detection of six active and repressive histone modifications and their ratios and combinatorial patterns on millions of individual nucleosomes by single-molecule imaging. In addition, our system provides sensitive and quantitative data on plasma proteins, including detection of non-secreted tumor-specific proteins, such as mutant p53. EPINUC analysis of a cohort of 63 colorectal cancer, 10 pancreatic cancer and 33 healthy plasma samples detected cancer with high accuracy and sensitivity, even at early stages. Finally, combining EPINUC with direct single-molecule DNA sequencing revealed the tissue of origin of colorectal, pancreatic, lung and breast tumors. EPINUC provides multilayered information of potential clinical relevance from limited (<1 ml) liquid biopsy material.
Identifiants
pubmed: 36076083
doi: 10.1038/s41587-022-01447-3
pii: 10.1038/s41587-022-01447-3
doi:
Substances chimiques
Biomarkers, Tumor
0
Cell-Free Nucleic Acids
0
Neoplasm Proteins
0
Nucleosomes
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
212-221Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Wan, J. C. M. et al. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nat. Rev. Cancer 17, 223–238 (2017).
pubmed: 28233803
doi: 10.1038/nrc.2017.7
Bronkhorst, A. J., Ungerer, V. & Holdenrieder, S. The emerging role of cell-free DNA as a molecular marker for cancer management. Biomol. Detect. Quantif. 17, 100087 (2019).
pubmed: 30923679
pmcid: 6425120
doi: 10.1016/j.bdq.2019.100087
Heitzer, E., Haque, I. S., Roberts, C. E. S. & Speicher, M. R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat. Rev. Genet. 20, 71–88 (2019).
pubmed: 30410101
doi: 10.1038/s41576-018-0071-5
Lo, Y. M. D., Han, D. S. C., Jiang, P. & Chiu, R. W. K. Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies. Science 372, eaaw3616 (2021).
pubmed: 33833097
doi: 10.1126/science.aaw3616
Xu, R. H. et al. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma. Nat. Mater. 16, 1155–1162 (2017).
pubmed: 29035356
doi: 10.1038/nmat4997
Moss, J. et al. Comprehensive human cell-type methylation atlas reveals origins of circulating cell-free DNA in health and disease. Nat. Commun. 9, 5068 (2018).
pubmed: 30498206
pmcid: 6265251
doi: 10.1038/s41467-018-07466-6
Kang, S. et al. CancerLocator: non-invasive cancer diagnosis and tissue-of-origin prediction using methylation profiles of cell-free DNA. Genome Biol. 18, 53 (2017).
Shen, S. Y. et al. Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Nature 563, 579–583 (2018).
pubmed: 30429608
doi: 10.1038/s41586-018-0703-0
Reinberg, D. & Vales, L. D. Chromatin domains rich in inheritance only certain histone posttranslational modifications qualify as being epigenetic. Science 361, 33–34 (2018).
pubmed: 29976815
doi: 10.1126/science.aat7871
Shema, E., Bernstein, B. E. & Buenrostro, J. D. Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution. Nat. Genet. 51, 19–25 (2019).
pubmed: 30559489
doi: 10.1038/s41588-018-0290-x
Allis, C. D. & Jenuwein, T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17, 487–500 (2016).
pubmed: 27346641
doi: 10.1038/nrg.2016.59
Mancarella, D. & Plass, C. Epigenetic signatures in cancer: proper controls, current challenges and the potential for clinical translation. Genome Med. 13, 23 (2021).
Sadeh, R. et al. ChIP–seq of plasma cell-free nucleosomes identifies gene expression programs of the cells of origin. Nat. Biotechnol. 39, 586–598 (2021).
pubmed: 33432199
pmcid: 7610786
doi: 10.1038/s41587-020-00775-6
Gezer, U. et al. Histone methylation marks on circulating nucleosomes as novel blood-based biomarker in colorectal cancer. Int. J. Mol. Sci. 16, 29654–29662 (2015).
pubmed: 26690425
pmcid: 4691123
doi: 10.3390/ijms161226180
Van den Ackerveken, P. et al. A novel proteomics approach to epigenetic profiling of circulating nucleosomes. Sci. Rep. 11, 7256 (2021).
Snyder, M. W., Kircher, M., Hill, A. J., Daza, R. M. & Shendure, J. Cell-free DNA comprises an in vivo nucleosome footprint that informs its tissues-of-origin. Cell 164, 57–68 (2016).
pubmed: 26771485
pmcid: 4715266
doi: 10.1016/j.cell.2015.11.050
Ulz, P. et al. Inferring expressed genes by whole-genome sequencing of plasma DNA. Nat. Genet. 48, 1273–1278 (2016).
pubmed: 27571261
doi: 10.1038/ng.3648
Sun, K. et al. Orientation-aware plasma cell-free DNA fragmentation analysis in open chromatin regions informs tissue of origin. Genome Res. 29, 418–427 (2019).
pubmed: 30808726
pmcid: 6396422
doi: 10.1101/gr.242719.118
Ferlay, J. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136, E359–E386 (2015).
pubmed: 25220842
doi: 10.1002/ijc.29210
Hu, Z. et al. Quantitative evidence for early metastatic seeding in colorectal cancer. Nat. Genet. 51, 1113–1122 (2019).
pubmed: 31209394
pmcid: 6982526
doi: 10.1038/s41588-019-0423-x
Shema, E. et al. Single-molecule decoding of combinatorially modified nucleosomes. Science 352, 717–721 (2016).
pubmed: 27151869
pmcid: 4904710
doi: 10.1126/science.aad7701
Heintzman, N. D. et al. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat. Genet. 39, 311–318 (2007).
pubmed: 17277777
doi: 10.1038/ng1966
Barski, A. et al. High-resolution profiling of histone methylations in the human genome. Cell 129, 823–837 (2007).
pubmed: 17512414
doi: 10.1016/j.cell.2007.05.009
Tiernan, J. P. et al. Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting. Br. J. Cancer 108, 662–667 (2013).
pubmed: 23322207
pmcid: 3593555
doi: 10.1038/bjc.2012.605
Meng, C. et al. TIMP-1 is a novel serum biomarker for the diagnosis of colorectal cancer: a meta-analysis. PLoS ONE 13, e0207039 (2018).
pubmed: 30458003
pmcid: 6245680
doi: 10.1371/journal.pone.0207039
Yu, J. et al. Identification of MST1 as a potential early detection biomarker for colorectal cancer through a proteomic approach. Sci. Rep. 7, 14265 (2017).
pubmed: 29079854
pmcid: 5660227
doi: 10.1038/s41598-017-14539-x
Mandal, S. et al. Direct kinetic fingerprinting for high-accuracy single-molecule counting of diverse disease biomarkers. Acc. Chem. Res. 54, 388–402 (2021).
Furth, N. et al. Unified platform for genetic and serological detection of COVID-19 with single-molecule technology. PLoS ONE 16, e0255096 (2021).
pubmed: 34310620
pmcid: 8312974
doi: 10.1371/journal.pone.0255096
Nakayama, M. & Oshima, M. Mutant p53 in colon cancer. J. Mol. Cell. Biol. 11, 267–276 (2019).
pubmed: 30496442
doi: 10.1093/jmcb/mjy075
Jung, G., Hernández-Illán, E., Moreira, L., Balaguer, F. & Goel, A. Epigenetics of colorectal cancer: biomarker and therapeutic potential. Nat. Rev. Gastroenterol. Hepatol. 17, 111–130 (2020).
pubmed: 31900466
pmcid: 7228650
doi: 10.1038/s41575-019-0230-y
Dawson, M. A. The cancer epigenome: concepts, challenges, and therapeutic opportunities. Science 355, 1147–1152 (2017).
pubmed: 28302822
doi: 10.1126/science.aam7304
Wood, K. H. & Zhou, Z. Emerging molecular and biological functions of MBD2, a reader of DNA methylation. Front. Genet. 7, 93 (2016).
pubmed: 27303433
pmcid: 4880565
doi: 10.3389/fgene.2016.00093
Bettegowda, C. et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci. Transl. Med. 6, 224ra24 (2014).
pubmed: 24553385
pmcid: 4017867
doi: 10.1126/scitranslmed.3007094
Brown, R., Curry, E., Magnani, L., Wilhelm-Benartzi, C. S. & Borley, J. Poised epigenetic states and acquired drug resistance in cancer. Nat. Rev. Cancer 14, 747–753 (2014).
pubmed: 25253389
doi: 10.1038/nrc3819
Kerachian, M. A. et al. Crosstalk between DNA methylation and gene expression in colorectal cancer, a potential plasma biomarker for tracing this tumor. Sci. Rep. 10, 2813 (2020).
King, W. D. et al. A cross-sectional study of global DNA methylation and risk of colorectal adenoma. BMC Cancer 14, 488 (2014).
pubmed: 24998982
pmcid: 4227295
doi: 10.1186/1471-2407-14-488
Frederiksen, C. et al. Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer. Ann. Oncol. 22, 369–375 (2011).
pubmed: 20643864
doi: 10.1093/annonc/mdq354
Garrido-Laguna, I. & Hidalgo, M. Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. Nat. Rev. Clin. Oncol. 12, 319–334 (2015).
pubmed: 25824606
doi: 10.1038/nrclinonc.2015.53
Lubotzky, A. et al. Liquid biopsy reveals collateral tissue damage in cancer. JCI Insight 7, e153559 (2022).
pubmed: 35076021
pmcid: 8855834
doi: 10.1172/jci.insight.153559
Gai, W. et al. Liver- and colon-specific DNA methylation markers in plasma for investigation of colorectal cancers with or without liver metastases. Clin. Chem. 64, 1239–1249 (2018).
pubmed: 29903871
doi: 10.1373/clinchem.2018.290304
Tannapfel, A. & Reinacher-Schick, A. Chemotherapy associated hepatotoxicity in the treatment of advanced colorectal cancer (CRC). Z. Gastroenterol. 46, 435–440 (2008).
pubmed: 18461519
doi: 10.1055/s-2008-1027151
Li, W. et al. 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers. Cell Res. 27, 1243–1257 (2017).
pubmed: 28925386
pmcid: 5630683
doi: 10.1038/cr.2017.121
Lio, C. W. J., Yuita, H. & Rao, A. Dysregulation of the TET family of epigenetic regulators in lymphoid and myeloid malignancies. Blood 134, 1487–1497 (2019).
pubmed: 31467060
pmcid: 6839946
doi: 10.1182/blood.2019791475
Zhang, L. et al. Tet-mediated covalent labelling of 5-methylcytosine for its genome-wide detection and sequencing. Nat. Commun. 4, 1517 (2013).
pubmed: 23443545
doi: 10.1038/ncomms2527
Song, C. X. et al. 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages. Cell Res. 27, 1231–1242 (2017).
pubmed: 28820176
pmcid: 5630676
doi: 10.1038/cr.2017.106
Newman, A. M. et al. Integrated digital error suppression for improved detection of circulating tumor DNA. Nat. Biotechnol. 34, 547–555 (2016).
pubmed: 27018799
pmcid: 4907374
doi: 10.1038/nbt.3520
Lisanti, S. et al. Comparison of methods for quantification of global DNA methylation in human cells and tissues. PLoS ONE 8, 79044 (2013).
doi: 10.1371/journal.pone.0079044
Bock, C. et al. Quantitative comparison of DNA methylation assays for biomarker development and clinical applications. Nat. Biotechnol. 34, 726–737 (2016).
doi: 10.1038/nbt.3605
Chandradoss, S. D. et al. Surface passivation for single-molecule protein studies. J. Vis. Exp. 2014, 50549 (2014).
Fleischhacker, M. & Schmidt, B. Circulating nucleic acids (CNAs) and cancer—a survey. Biochim. Biophys. Acta 1775, 181–232 (2007).
pubmed: 17137717
Harris, T. D. et al. Single-molecule DNA sequencing of a viral genome. Science 320, 106–109 (2008).
pubmed: 18388294
doi: 10.1126/science.1150427
Kim, K. L. et al. Systematic detection of m
pubmed: 34734208
pmcid: 8562683
doi: 10.1016/j.crmeth.2021.100061