Liquid biopsy explained

Liquid biopsy
Purpose:analysis of non-solid biological tissue
Synonyms:Fluid biopsy

A liquid biopsy, also known as fluid biopsy or fluid phase biopsy, is the sampling and analysis of non-solid biological tissue, primarily blood.[1] [2] Like traditional biopsy, this type of technique is mainly used as a diagnostic and monitoring tool for diseases such as cancer, with the added benefit of being largely non-invasive. Liquid biopsies may also be used to validate the efficiency of a cancer treatment drug by taking multiple samples in the span of a few weeks. The technology may also prove beneficial for patients after treatment to monitor relapse.[3]

The clinical implementation of liquid biopsies is not yet widespread but is becoming standard of care in some areas.[4]

Liquid biopsy refers to the molecular analysis in biological fluids of nucleic acids, subcellular structures, especially exosomes, and, in the context of cancer, circulating tumor cells.[5]

Types

There are several types of liquid biopsy methods; method selection depends on the condition that is being studied.

DiseaseTissue sampledSampling procedureInvasivenessSubstance isolatedIsolation and detection methodAnalysisRefs
Cancer (various) Blood Minimally invasive Circulating tumor cells (CTCs) Various (e.g. CellSearch, RosetteStep, Dynabeads) Flow cytometry, nucleic acid extraction, immunocytochemistry, functional assays [6] [7] [8] [9]
Cancer (various) Blood Phlebotomy Minimally invasive Circulating tumor DNA (ctDNA) [10] [11] [12]
Urine Urine collection Non-invasive Urinary tumor DNA (utDNA) DNA extraction Next-generation sequencing [13] [14]
Non-urological cancers Urine Urine collection Non-invasive Urine proteins, metabolites [15] [16]
Bladder and prostate cancerUrineUrine collectionNon-invasiveExfoliated cancer cellsUrinalysisFluorescence in situ hybridization[17] [18]
Blood Phlebotomy Minimally invasive Circulating endothelial cells (CECs) Various (e.g. CellSearch, HD-CEC)Flow cytometry [19]
Neurological diseases Invasive CSF proteins, nucleic acids VariousELISA, multiplex assay, next-generation sequencing [20] [21]
Blood (maternal) Phlebotomy Minimally invasive Cell-free fetal DNA (cffDNA) DNA extraction [22]
Prenatal diagnosis Blood (maternal) Phlebotomy Minimally invasive Fetal cells in maternal blood (FCMB) Flow cytometry Karyotyping, fluorescent in situ hybridization [23]
Prenatal diagnosis Blood (umbilical cord) Invasive Umbilical blood cells and molecules Various Karyotyping, blood typing, blood tests, Kleihauer–Betke test, flow cytometry [24]
Prenatal diagnosis Invasive Amniotic fluid cells and molecules Various [25]

A wide variety of biomarkers may be studied to detect or monitor other diseases. For example, isolation of protoporphyrin IX from blood samples can be used as a diagnostic tool for atherosclerosis.[26] Cancer biomarkers in the blood include PSA (prostate cancer), CA19-9 (pancreatic cancer) and CA-125 (ovarian cancer).

Mechanism

Circulating tumor DNA (ctDNA) refers to DNA released by cancerous cells into the blood stream.[27] [28] Cancer mutations in ctDNA mirror those found in traditional tumor biopsies, which allows them to be used as molecular biomarkers to track the disease.[29] [30] These tests can have sensitive limits of detection, allowing monitoring of minimal residual disease after treatment. Scientists can purify and analyze ctDNA using next-generation sequencing (NGS) or PCR-based methods such as digital PCR.[31] NGS-based methods provide a comprehensive view of a cancer’s genetic makeup and is especially useful in diagnosis while digital PCR offers a more targeted approach especially well-suited for detecting minimal residual disease and for monitoring treatment response and disease progression.[32] [33] Recent progress in epigenetics has expanded the use of liquid biopsy for the detection of early-stage cancers, including by approaches such as Cancer Likelihood in Plasma (CLiP) .[34]

Liquid biopsies can detect changes in tumor burden months or years before conventional imaging tests can, making them suitable for early tumor detection, monitoring, and detection of resistance mutations.[35] [36] [37] The increase in the adoption of NGS in various research fields, advancement in NGS, and increase in the adoption of personalized medicine are expected to drive growth in the global liquid biopsy market.[38]

Clinical application

In cancer, liquid biopsy can be used for either multi-cancer screening tests,[39] when solid tumor biopsies are not possible, to compare different treatments as part of clinical trials, to inform decisions for doctors/patients on which precision medicine treatment to select, and for minimal residual disease detection (disease monitoring). Liquid biopsy of circulating tumor DNA for EGFR-mutated lung cancer is approved by the FDA.[40]

The CellSearch method for enumeration of circulating tumor cells in metastatic breast, metastatic colon, and metastatic prostate cancer has been validated and approved by the FDA as a useful prognostic method.[41]

See also

Notes and References

  1. Alix-Panabières. Catherine. Pantel. Klaus. January 2013. Circulating tumor cells: liquid biopsy of cancer. Clinical Chemistry. 59. 1. 110–118. 10.1373/clinchem.2012.194258. 1530-8561. 23014601. free.
  2. Crowley. Emily. Di Nicolantonio. Federica. Loupakis. Fotios. Alberto Bardelli. Bardelli. Alberto. Liquid biopsy: monitoring cancer-genetics in the blood. Nature Reviews Clinical Oncology. 9 July 2013. 10. 8. 472–484. 10.1038/nrclinonc.2013.110. 23836314. 25537784.
  3. News: Understanding cancer's unruly origins helps early diagnosis . September 14, 2017 . The Economist. 2017-09-29.
  4. Gingras. Isabelle. Salgado. Roberto. Ignatiadis. Michail. November 2015. Liquid biopsy: will it be the 'magic tool' for monitoring response of solid tumors to anticancer therapies?. Current Opinion in Oncology. 27. 6. 560–567. 10.1097/CCO.0000000000000223. 26335664. 13339984.
  5. Web site: Liquid Biopsy - an overview ScienceDirect Topics . 2023-11-08 . www.sciencedirect.com.
  6. Peeters . D J E . De Laere . B . Van den Eynden . G G . Van Laere . S J . Rothé . F . Ignatiadis . M . Sieuwerts . A M . Lambrechts . D . Rutten . A . van Dam . P A . Pauwels . P . Peeters . M . Vermeulen . P B . Dirix . L Y . Semiautomated isolation and molecular characterisation of single or highly purified tumour cells from CellSearch enriched blood samples using dielectrophoretic cell sorting . British Journal of Cancer . April 2013 . 108 . 6 . 1358–1367 . 10.1038/bjc.2013.92. 23470469 . 3619252 .
  7. Agerbæk . Mette Ø. . Bang-Christensen . Sara R. . Yang . Ming-Hsin . Clausen . Thomas M. . Pereira . Marina A. . Sharma . Shreya . Ditlev . Sisse B. . Nielsen . Morten A. . Choudhary . Swati . Gustavsson . Tobias . Sorensen . Poul H. . Meyer . Tim . Propper . David . Shamash . Jonathan . Theander . Thor G. . Aicher . Alexandra . Daugaard . Mads . Heeschen . Christopher . Salanti . Ali . The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner . Nature Communications . December 2018 . 9 . 1 . 3279 . 10.1038/s41467-018-05793-2. 30115931 . 6095877 . 2018NatCo...9.3279A .
  8. Book: Thiele . Jana- A. . Pitule . Pavel . Hicks . James . Kuhn . Peter . Tumor Profiling . Single-Cell Analysis of Circulating Tumor Cells . Methods in Molecular Biology . 2019 . 1908 . 243–264 . 10.1007/978-1-4939-9004-7_17. 30649733 . 7679177 . 978-1-4939-9002-3 .
  9. Nakazawa . M. . Lu . C. . Chen . Y. . Paller . C. J. . Carducci . M. A. . Eisenberger . M. A. . Luo . J. . Antonarakis . E. S. . 2015-09-01 . Serial blood-based analysis of AR-V7 in men with advanced prostate cancer . Annals of Oncology . 26 . 9 . 1859–1865 . 10.1093/annonc/mdv282 . 0923-7534. 4551160 .
  10. Heitzer. E.. Ulz. P.. Geigl. J. B.. Circulating Tumor DNA as a Liquid Biopsy for Cancer. Clinical Chemistry. 11 November 2014. 61. 1. 112–123. 10.1373/clinchem.2014.222679. 25388429. free.
  11. Wan. Jonathan C. M.. Massie. Charles. Garcia-Corbacho. Javier. Mouliere. Florent. Brenton. James D.. Caldas. Carlos. Pacey. Simon. Baird. Richard. Rosenfeld. Nitzan. Liquid biopsies come of age: towards implementation of circulating tumour DNA. Nature Reviews Cancer. 17. 4. 223–238. 24 February 2017. 10.1038/nrc.2017.7. 28233803. 4561229.
  12. Avanzini S, Kurtz DM, Chabon JJ, Moding EJ, Hori SS, Gambhir SS, Alizadeh AA, Diehn M, Reiter JG . A mathematical model of ctDNA shedding predicts tumor detection size . Science Advances . 6 . 50 . eabc4308 . December 2020 . 33310847 . 10.1126/sciadv.abc4308 . 7732186 . 2020SciA....6.4308A . 228096858 . free .
  13. Chaudhuri . Aadel A. . Pellini . Bruna . Pejovic . Nadja . Chauhan . Pradeep S. . Harris . Peter K. . Szymanski . Jeffrey J. . Smith . Zachary L. . Arora . Vivek K. . Emerging Roles of Urine-Based Tumor DNA Analysis in Bladder Cancer Management . JCO Precision Oncology . November 2020 . 4 . 4 . 806–817 . 10.1200/PO.20.00060. 32923907 . 7448529 .
  14. Bicocca . Vincent T. . Phillips . Kevin G. . Fischer . Daniel S. . Caruso . Vincent M. . Goudarzi . Mahdi . Garcia-Ransom . Monica . Lentz . Peter S. . MacBride . Andrew R. . Jensen . Brad W. . Mazzarella . Brian C. . Koppie . Theresa . Korkola . James E. . Gray . Joe W. . Levin . Trevor G. . September 2022 . Urinary Comprehensive Genomic Profiling Correlates Urothelial Carcinoma Mutations with Clinical Risk and Efficacy of Intervention . Journal of Clinical Medicine . en . 11 . 19 . 5827 . 10.3390/jcm11195827 . 36233691 . 9571552 . 2077-0383. free .
  15. Ward . DG . Nyangoma . S . Joy . H . Hamilton . E . Wei . W . Tselepis . C . Steven . N . Wakelam . MJ . Johnson . PJ . Ismail . T . Martin . A . Proteomic profiling of urine for the detection of colon cancer. . Proteome Science . 16 June 2008 . 6 . 19 . 10.1186/1477-5956-6-19 . 18558005. 2440369 . free .
  16. Arasaradnam . RP . Wicaksono . A . O'Brien . H . Kocher . HM . Covington . JA . Crnogorac-Jurcevic . T . Noninvasive Diagnosis of Pancreatic Cancer Through Detection of Volatile Organic Compounds in Urine. . Gastroenterology . February 2018 . 154 . 3 . 485–487.e1 . 10.1053/j.gastro.2017.09.054 . 29129714. free .
  17. Halling . Kevin C. . Kipp . Benjamin R. . September 2008 . Bladder Cancer Detection Using FISH (UroVysion Assay) . Advances in Anatomic Pathology . en . 15 . 5 . 279–286 . 10.1097/PAP.0b013e3181832320 . 1072-4109.
  18. Eskra . Jillian N. . Rabizadeh . Daniel . Mangold . Leslie . Fabian . Elizabeth . Brennen . W. Nathaniel . Yeater . David B. . Pienta . Kenneth J. . Partin . Alan W. . Isaacs . William B. . Pavlovich . Christian P. . Luo . Jun . 2020-08-20 . A novel method for detection of exfoliated prostate cancer cells in urine by RNA in situ hybridization . Prostate Cancer and Prostatic Diseases . en . 24 . 1 . 220–232 . 10.1038/s41391-020-00272-6 . 1365-7852.
  19. Bethel . Kelly . Luttgen . Madelyn S . Damani . Samir . Kolatkar . Anand . Lamy . Rachelle . Sabouri-Ghomi . Mohsen . Topol . Sarah . Topol . Eric J . Kuhn . Peter . Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction . Physical Biology . 9 January 2014 . 11 . 1 . 016002 . 10.1088/1478-3975/11/1/016002. 24406475 . 4143170 . 2014PhBio..11a6002B .
  20. Pyykkö. Okko T.. Lumela. Miikka. Rummukainen. Jaana. Nerg. Ossi. Seppälä. Toni T.. Herukka. Sanna-Kaisa. Koivisto. Anne M.. Alafuzoff. Irina. Puli. Lakshman. Savolainen. Sakari. Soininen. Hilkka. Jääskeläinen. Juha E.. Hiltunen. Mikko. Zetterberg. Henrik. Leinonen. Ville. Fiandaca. Massimo S.. Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus. PLOS ONE. 17 March 2014. 9. 3. e91974. 10.1371/journal.pone.0091974. 24638077. 3956805. 2014PLoSO...991974P. free.
  21. 6284385 . 30401727 . 10.15252/emmm.201809323 . 10 . 12 . e9323 . Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients . 2018 . Mouliere F, Mair R, Chandrananda D, Marass F, Smith CG, Su J, Morris J, Watts C, Brindle KM, Rosenfeld N . EMBO Mol Med.
  22. Rafi . Imran . Hill . Melissa . Hayward . Judith . Chitty . Lyn S . Non-invasive prenatal testing: use of cell-free fetal DNA in Down syndrome screening . British Journal of General Practice . July 2017 . 67 . 660 . 298–299 . 10.3399/bjgp17X691625. 28663415 . 5565870 .
  23. Singh . Ripudaman . Hatt . Lotte . Ravn . Katarina . Vogel . Ida . Petersen . Olav Bjørn . Uldbjerg . Niels . Schelde . Palle . Fetal cells in maternal blood for prenatal diagnosis: a love story rekindled . Biomarkers in Medicine . September 2017 . 11 . 9 . 705–710 . 10.2217/bmm-2017-0055. 28617034 . free .
  24. Book: Weiner . Carl P. . Lee . Gene T. . Joseph J. . Anthony M. . Vincenzo . Jesus R. . Apuzzio . Vintzileos . Berghella . Alvarez-Perez . Operative Obstetrics, 4E . 2017 . Routledge . 978-1-4987-2056-4 . Cordocentesis. 10.1201/9781315382739 .
  25. Book: Perni . Sriram C. . Roost . John R. . Chervenak. Frank A. . Joseph J. . Anthony M. . Vincenzo . Jesus R. . Apuzzio . Vintzileos . Berghella . Alvarez-Perez . Operative Obstetrics, 4E . 2017 . Routledge . 978-1-4987-2056-4 . Amniocentesis. 10.1201/9781315382739 .
  26. Nascimento da Silva. Monica. Sicchieri. Letícia Bonfante. Rodrigues de Oliveira Silva. Flávia. Andrade. Maira Franco. Courrol. Lilia Coronato. Liquid biopsy of atherosclerosis using protoporphyrin IX as a biomarker. The Analyst. 2014. 139. 6. 1383–8. 10.1039/c3an01945d. 24432352. 2014Ana...139.1383N. 25707729 .
  27. Web site: What is circulating tumor DNA and how is it used to diagnose and manage cancer?: MedlinePlus Genetics. 2021-09-03. medlineplus.gov. en.
  28. https://ghr.nlm.nih.gov/primer/testing/circulatingtumordna "What is circulating tumor DNA and how is it used to diagnose and manage cancer? "
  29. http://oncpracticemanagement.com/issue-archive/2016/july-2016-vol-6-no-7/liquid-biopsies-show-high-correlation-with-tissue-biopsy-for-genetic-mutations/ "Liquid Biopsies Show High Correlation with Tissue Biopsy for Genetic Mutations"
  30. https://evcna.com/article/view/5081/ "Cell-free DNA as a biomarker in cancer"
  31. Picher, Andy."Liquid Biopsy, Key for Precision Medicine". Genetic Engineering & Biotechnology News. 23 July 2018. Retrieved 12 March 2019.
  32. https://www.onclive.com/insights/liquid-biopsy-nsclc/liquid-biopsy-differences-among-technologies "Liquid Biopsy: Differences Among Technologies"
  33. Ellis, Jen."dPCR: The Emergence of the Digital Age". Biocompare. 7 May 2018. Retrieved 12 March 2019.
  34. 31614115 . 10.1016/j.ccell.2019.09.003 . 36 . 4 . 350–368 . Toward the early detection of cancer by decoding the epigenetic and environmental fingerprints of cell-free DNA . 2019 . van der Pol Y, Mouliere F . Cancer Cell. free .
  35. McDowell, Sandy."Liquid Biopsies: Past, Present, and Future". American Cancer Society. 12 February 2018. Retrieved 12 March 2019.
  36. https://www.cancer.gov/news-events/cancer-currents-blog/2017/liquid-biopsy-detects-treats-cancer "Liquid Biopsy: Using DNA in Blood to Detect, Track, and Treat Cancer"
  37. Olsson . Eleonor . Winter . Christof . 2015 . Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease . EMBO Molecular Medicine . 7 . 8 . 1034–1047 . 10.15252/emmm.201404913 . 25987569 . 4551342 .
  38. Web site: Liquid Biopsy Market - A Global and Regional Analysis: Focus on Offering, Usage, Workflow, Circulating Biomarker, Sample, Technology, Clinical Application, End User, and Region - Analysis and Forecast, 2022-2032 . 2022-09-19 . bisresearch.com . en.
  39. Brito-Rocha . Tiago . Constâncio . Vera . Henrique . Rui . Jerónimo . Carmen . Shifting the Cancer Screening Paradigm: The Rising Potential of Blood-Based Multi-Cancer Early Detection Tests . Cells . 18 March 2023 . 12 . 6 . 935 . 10.3390/cells12060935 . free . 36980276 . 10047029 . 2073-4409.
  40. Kwapisz. Dorota. February 2017. The first liquid biopsy test approved. Is it a new era of mutation testing for non-small cell lung cancer?. Annals of Translational Medicine. 5. 3. 46. 10.21037/atm.2017.01.32. 2305-5839. 5326656. 28251125 . free .
  41. Karachaliou. N. Mayo-de-Las-Casas. C. Molina-Vila. MA. Rosell. R. March 2015. Real-time liquid biopsies become a reality in cancer treatment.. Annals of Translational Medicine. 3. 3. 36. 10.3978/j.issn.2305-5839.2015.01.16. 4356857. 25815297.

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