Liquid biopsy

Last updated
Liquid biopsy
Synonyms Fluid biopsy
Purposeanalysis of non-solid biological tissue

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]

Contents

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 Phlebotomy 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)BloodPhlebotomyMinimally invasive Circulating tumor DNA (ctDNA) DNA extraction Next-generation sequencing [10] [11] [12]
Urothelial carcinoma UrineUrine collectionNon-invasiveUrinary tumor DNA (utDNA)DNA extractionNext-generation sequencing [13] [14]
Non-urological cancersUrineUrine collectionNon-invasiveUrine proteins, metabolites HPLC-MS Proteomics, metabolomics [15] [16]
Bladder and prostate cancerUrineUrine collectionNon-invasiveExfoliated cancer cells Urinalysis Fluorescence in situ hybridization [17] [18]
Heart attack BloodPhlebotomyMinimally invasive Circulating endothelial cells (CECs)Various (e.g. CellSearch, HD-CEC)Flow cytometry [19]
Neurological diseases Cerebrospinal fluid Lumbar puncture InvasiveCSF proteins, nucleic acidsVarious ELISA, multiplex assay, next-generation sequencing [20] [21]
Prenatal diagnosis Blood (maternal)PhlebotomyMinimally invasive Cell-free fetal DNA (cffDNA)DNA extraction Karyotyping, fluorescent in situ hybridization [22]
Prenatal diagnosisBlood (maternal)PhlebotomyMinimally invasiveFetal cells in maternal blood (FCMB)Flow cytometryKaryotyping, fluorescent in situ hybridization [23]
Prenatal diagnosisBlood (umbilical cord) Cordocentesis InvasiveUmbilical blood cells and moleculesVariousKaryotyping, blood typing, blood tests, Kleihauer–Betke test, flow cytometry [24]
Prenatal diagnosis Amniotic fluid Amniocentesis InvasiveAmniotic fluid cells and moleculesVariousKaryotyping, blood typing, L/S ratio, S/A ratio [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

Related Research Articles

<span class="mw-page-title-main">Biopsy</span> Medical test involving extraction of sample cells or tissues for examination

A biopsy is a medical test commonly performed by a surgeon, an interventional radiologist, or an interventional cardiologist. The process involves the extraction of sample cells or tissues for examination to determine the presence or extent of a disease. The tissue is then fixed, dehydrated, embedded, sectioned, stained and mounted before it is generally examined under a microscope by a pathologist; it may also be analyzed chemically. When an entire lump or suspicious area is removed, the procedure is called an excisional biopsy. An incisional biopsy or core biopsy samples a portion of the abnormal tissue without attempting to remove the entire lesion or tumor. When a sample of tissue or fluid is removed with a needle in such a way that cells are removed without preserving the histological architecture of the tissue cells, the procedure is called a needle aspiration biopsy. Biopsies are most commonly performed for insight into possible cancerous or inflammatory conditions.

A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers. They can be found in bodily fluids or tissue. Markers can help with assessing prognosis, surveilling patients after surgical removal of tumors, and even predicting drug-response and monitor therapy.

In medicine, a biomarker is a measurable indicator of the severity or presence of some disease state. It may be defined as a "cellular, biochemical or molecular alteration in cells, tissues or fluids that can be measured and evaluated to indicate normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention." More generally a biomarker is anything that can be used as an indicator of a particular disease state or some other physiological state of an organism. According to the WHO, the indicator may be chemical, physical, or biological in nature - and the measurement may be functional, physiological, biochemical, cellular, or molecular.

Noninvasive genotyping is a modern technique for obtaining DNA for genotyping that is characterized by the indirect sampling of specimen, not requiring harm to, handling of, or even the presence of the organism of interest. Beginning in the early 1990s, with the advent of PCR, researchers have been able to obtain high-quality DNA samples from small quantities of hair, feathers, scales, or excrement. These noninvasive samples are an improvement over older allozyme and DNA sampling techniques that often required larger samples of tissue or the destruction of the studied organism. Noninvasive genotyping is widely utilized in conservation efforts, where capture and sampling may be difficult or disruptive to behavior. Additionally, in medicine, this technique is being applied in humans for the diagnosis of genetic disease and early detection of tumors. In this context, invasivity takes on a separate definition where noninvasive sampling also includes simple blood samples.

Digital polymerase chain reaction is a biotechnological refinement of conventional polymerase chain reaction methods that can be used to directly quantify and clonally amplify nucleic acids strands including DNA, cDNA, or RNA. The key difference between dPCR and qPCR lies in the method of measuring nucleic acids amounts, with the former being a more precise method than PCR, though also more prone to error in the hands of inexperienced users. PCR carries out one reaction per single sample. dPCR also carries out a single reaction within a sample, however the sample is separated into a large number of partitions and the reaction is carried out in each partition individually. This separation allows a more reliable collection and sensitive measurement of nucleic acid amounts. The method has been demonstrated as useful for studying variations in gene sequences—such as copy number variants and point mutations.

Minimal residual disease (MRD), also known as Molecular residual disease, is the name given to small numbers of cancer cells that remain in a person either during or after treatment when the patient is in remission. Sensitive molecular tests are either in development or available to test for MRD. These can measure minute levels of cancer cells in tissue samples, sometimes as low as one cancer cell in a million normal cells, either using DNA, RNA or proteins.

<span class="mw-page-title-main">Circulating tumor cell</span> Cell from a primary tumor carried by blood circulation

A circulating tumor cell (CTC) is a cancer cell from a primary tumor that has shed into the blood of the circulatory system, or the lymph of the lymphatic system. CTCs are carried around the body to other organs where they may leave the circulation and become the seeds for the subsequent growth of secondary tumors. This is known as metastasis, responsible for most cancer-related deaths.

<span class="mw-page-title-main">Cancer biomarker</span> Substance or process that is indicative of the presence of cancer in the body

A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.

<span class="mw-page-title-main">Circulating tumor DNA</span> Tumor-derived fragmented DNA in the bloodstream

Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA in the bloodstream that is not associated with cells. ctDNA should not be confused with cell-free DNA (cfDNA), a broader term which describes DNA that is freely circulating in the bloodstream, but is not necessarily of tumor origin. Because ctDNA may reflect the entire tumor genome, it has gained traction for its potential clinical utility; "liquid biopsies" in the form of blood draws may be taken at various time points to monitor tumor progression throughout the treatment regimen.

CAPP-Seq is a next-generation sequencing based method used to quantify circulating DNA in cancer (ctDNA). The method was introduced in 2014 by Ash Alizadeh and Maximilian Diehn’s laboratories at Stanford, as a tool for measuring Cell-free tumor DNA which is released from dead tumor cells into the blood and thus may reflect the entire tumor genome. This method can be generalized for any cancer type that is known to have recurrent mutations. CAPP-Seq can detect one molecule of mutant DNA in 10,000 molecules of healthy DNA. The original method was further refined in 2016 for ultra sensitive detection through integration of multiple error suppression strategies, termed integrated Digital Error Suppression (iDES). The use of ctDNA in this technique should not be confused with circulating tumor cells (CTCs); these are two different entities.

Circulating free DNA (cfDNA) (also known as cell-free DNA) are degraded DNA fragments released to body fluids such as blood plasma, urine, cerebrospinal fluid, etc. Typical sizes of cfDNA fragments reflect chromatosome particles (~165bp), as well as multiples of nucleosomes, which protect DNA from digestion by apoptotic nucleases. The term cfDNA can be used to describe various forms of DNA freely circulating in body fluids, including circulating tumor DNA (ctDNA), cell-free mitochondrial DNA (ccf mtDNA), cell-free fetal DNA (cffDNA) and donor-derived cell-free DNA (dd-cfDNA). Elevated levels of cfDNA are observed in cancer, especially in advanced disease. There is evidence that cfDNA becomes increasingly frequent in circulation with the onset of age. cfDNA has been shown to be a useful biomarker for a multitude of ailments other than cancer and fetal medicine. This includes but is not limited to trauma, sepsis, aseptic inflammation, myocardial infarction, stroke, transplantation, diabetes, and sickle cell disease. cfDNA is mostly a double-stranded extracellular molecule of DNA, consisting of small fragments (50 to 200 bp) and larger fragments (21 kb) and has been recognized as an accurate marker for the diagnosis of prostate cancer and breast cancer.

Prognostic markers are biomarkers used to measure the progress of a disease in the patient sample. Prognostic markers are useful to stratify the patients into groups, guiding towards precise medicine discovery. The widely used prognostic markers in cancers include stage, size, grade, node and metastasis. In addition to these common markers, there are prognostic markers specific to different cancer types. For example estrogen level, progesterone and HER2 are markers specific to breast cancer patients. There is evidence showing that genes behaving as tumor suppressors or carcinogens could act as prognostic markers due to altered gene expression or mutation. Besides genetic biomarkers, there are also biomarkers that are detected in plasma or body fluid which can be metabolic or protein biomarkers.

Luis Alberto Diaz, Jr. is the Head of the Division of Solid Tumor Oncology in Memorial Sloan Kettering’s Department of Medicine.

Urinary cell-free DNA (ucfDNA) refers to DNA fragments in urine released by urogenital and non-urogenital cells. Shed cells on urogenital tract release high- or low-molecular-weight DNA fragments via apoptosis and necrosis, while circulating cell-free DNA (cfDNA) that passes through glomerular pores contributes to low-molecular-weight DNA. Most of the ucfDNA is low-molecular-weight DNA in the size of 150-250 base pairs. The detection of ucfDNA composition allows the quantification of cfDNA, circulating tumour DNA, and cell-free fetal DNA components. Many commercial kits and devices have been developed for ucfDNA isolation, quantification, and quality assessment.

Epitope Detection in Monocytes (EDIM) is a technology that uses the innate immune system's mechanisms to detect biomarkers or antigens in immune cells. It is a non-invasive form of liquid biopsy, i.e. biopsy from blood, which analyzes activated macrophages (CD14+/CD16+) for disease-specific epitopes, such as tumor cell components.

EPIC-seq,, is a high-throughput method that specifically targets gene promoters using cell-free DNA (cfDNA) sequencing. By employing non-invasive techniques such as blood sampling, it infers the expression levels of targeted genes. It consists of both wet and dry lab stages.

Nitzan Rosenfeld is a professor of Cancer Diagnostics at the University of Cambridge. He is a Senior Group Leader at the Cancer Research UK Cambridge Institute and co-founder of Inivata, a clinical cancer genomics company.

Focused-ultrasound-mediated diagnostics or FUS-mediated diagnostics are an area of clinical diagnostic tools that use ultrasound to detect diseases and cancers. Although ultrasound has been used for imaging in various settings, focused-ultrasound refers to the detection of specific cells and biomarkers under flow combining ultrasound with lasers, microbubbles, and imaging techniques. Current diagnostic techniques for detecting tumors and diseases using biopsies often include invasive procedures and require improved accuracy, especially in cases such as glioblastoma and melanoma. The field of FUS-mediated diagnostics targeting cells and biomarkers is being investigated for overcoming these limitations.

Alain Thierry is a French geneticist and cancer researcher. He specializes in the clinical applications of circulating DNA analysis, notably in cancer care management. He is currently Director of Research at the INSERM's Cancer Research Institute in Montpellier, France.

<span class="mw-page-title-main">MRNA-based disease diagnosis</span> Disease diagnosis using messenger RNA

mRNA-based disease diagnosis technologies are diagnostic procedures using messenger RNAs. as molecular diagnostic tools to discover the relationships between patient's DNAs and their specific biological features. The mRNA-based disease diagnosis technologies have been applied to medical field widely in recent years, especially on early diagnosis of tumors. The technology can be applied to various types of samples depending on how easily the samples are accessible and whether the samples reliably contain the mRNA that related to specific diseases. For example, in hepatocellular carcinoma, the tumor tissues excised during the operation are a good resource for mRNA-based test to analysis. Among those most commonly used samples, blood sample is one of the most easily accessible via minimally invasive method. degenerative diseases. Blood has been used in early diagnosis of some cancers, such as non-small lung cancer and neuroendocrine tumors.

References

  1. ↑ Alix-Panabières, Catherine; Pantel, Klaus (January 2013). "Circulating tumor cells: liquid biopsy of cancer". Clinical Chemistry. 59 (1): 110–118. doi: 10.1373/clinchem.2012.194258 . ISSN   1530-8561. PMID   23014601.
  2. ↑ Crowley, Emily; Di Nicolantonio, Federica; Loupakis, Fotios; Bardelli, Alberto (9 July 2013). "Liquid biopsy: monitoring cancer-genetics in the blood". Nature Reviews Clinical Oncology. 10 (8): 472–484. doi:10.1038/nrclinonc.2013.110. PMID   23836314. S2CID   25537784.
  3. ↑ "Understanding cancer's unruly origins helps early diagnosis". The Economist. September 14, 2017. Retrieved 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. doi:10.1097/CCO.0000000000000223. PMID   26335664. S2CID   13339984.
  5. ↑ "Liquid Biopsy - an overview | ScienceDirect Topics". www.sciencedirect.com. Retrieved 2023-11-08.
  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 (April 2013). "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. 108 (6): 1358–1367. doi:10.1038/bjc.2013.92. PMC   3619252 . PMID   23470469.
  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 (December 2018). "The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an EpCAM-independent manner". Nature Communications. 9 (1): 3279. Bibcode:2018NatCo...9.3279A. doi:10.1038/s41467-018-05793-2. PMC   6095877 . PMID   30115931.
  8. ↑ Thiele, Jana- A.; Pitule, Pavel; Hicks, James; Kuhn, Peter (2019). "Single-Cell Analysis of Circulating Tumor Cells". Tumor Profiling. Methods in Molecular Biology. Vol. 1908. pp. 243–264. doi:10.1007/978-1-4939-9004-7_17. ISBN   978-1-4939-9002-3. PMC   7679177 . PMID   30649733.
  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. doi:10.1093/annonc/mdv282. ISSN   0923-7534. PMC   4551160 . PMID   26117829.
  10. ↑ Heitzer, E.; Ulz, P.; Geigl, J. B. (11 November 2014). "Circulating Tumor DNA as a Liquid Biopsy for Cancer". Clinical Chemistry. 61 (1): 112–123. doi: 10.1373/clinchem.2014.222679 . PMID   25388429.
  11. ↑ Wan, Jonathan C. M.; Massie, Charles; Garcia-Corbacho, Javier; Mouliere, Florent; Brenton, James D.; Caldas, Carlos; Pacey, Simon; Baird, Richard; Rosenfeld, Nitzan (24 February 2017). "Liquid biopsies come of age: towards implementation of circulating tumour DNA". Nature Reviews Cancer. 17 (4): 223–238. doi:10.1038/nrc.2017.7. PMID   28233803. S2CID   4561229.
  12. ↑ Avanzini S, Kurtz DM, Chabon JJ, Moding EJ, Hori SS, Gambhir SS, Alizadeh AA, Diehn M, Reiter JG (December 2020). "A mathematical model of ctDNA shedding predicts tumor detection size". Science Advances. 6 (50): eabc4308. Bibcode:2020SciA....6.4308A. doi: 10.1126/sciadv.abc4308 . PMC   7732186 . PMID   33310847. S2CID   228096858.
  13. ↑ Chaudhuri, Aadel A.; Pellini, Bruna; Pejovic, Nadja; Chauhan, Pradeep S.; Harris, Peter K.; Szymanski, Jeffrey J.; Smith, Zachary L.; Arora, Vivek K. (November 2020). "Emerging Roles of Urine-Based Tumor DNA Analysis in Bladder Cancer Management". JCO Precision Oncology. 4 (4): 806–817. doi:10.1200/PO.20.00060. PMC   7448529 . PMID   32923907.
  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. 11 (19): 5827. doi: 10.3390/jcm11195827 . ISSN   2077-0383. PMC   9571552 . PMID   36233691.
  15. ↑ Ward, DG; Nyangoma, S; Joy, H; Hamilton, E; Wei, W; Tselepis, C; Steven, N; Wakelam, MJ; Johnson, PJ; Ismail, T; Martin, A (16 June 2008). "Proteomic profiling of urine for the detection of colon cancer". Proteome Science. 6: 19. doi: 10.1186/1477-5956-6-19 . PMC   2440369 . PMID   18558005.
  16. ↑ Arasaradnam, RP; Wicaksono, A; O'Brien, H; Kocher, HM; Covington, JA; Crnogorac-Jurcevic, T (February 2018). "Noninvasive Diagnosis of Pancreatic Cancer Through Detection of Volatile Organic Compounds in Urine". Gastroenterology. 154 (3): 485–487.e1. doi: 10.1053/j.gastro.2017.09.054 . PMID   29129714.
  17. ↑ Halling, Kevin C.; Kipp, Benjamin R. (September 2008). "Bladder Cancer Detection Using FISH (UroVysion Assay)". Advances in Anatomic Pathology. 15 (5): 279–286. doi:10.1097/PAP.0b013e3181832320. ISSN   1072-4109. PMID   18724101.
  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. 24 (1): 220–232. doi:10.1038/s41391-020-00272-6. ISSN   1365-7852. PMID   32820256.
  19. ↑ Bethel, Kelly; Luttgen, Madelyn S; Damani, Samir; Kolatkar, Anand; Lamy, Rachelle; Sabouri-Ghomi, Mohsen; Topol, Sarah; Topol, Eric J; Kuhn, Peter (9 January 2014). "Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction". Physical Biology. 11 (1): 016002. Bibcode:2014PhBio..11a6002B. doi:10.1088/1478-3975/11/1/016002. PMC   4143170 . PMID   24406475.
  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. (17 March 2014). "Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus". PLOS ONE. 9 (3): e91974. Bibcode:2014PLoSO...991974P. doi: 10.1371/journal.pone.0091974 . PMC   3956805 . PMID   24638077.
  21. ↑ Mouliere F, Mair R, Chandrananda D, Marass F, Smith CG, Su J, Morris J, Watts C, Brindle KM, Rosenfeld N (2018). "Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients". EMBO Mol Med. 10 (12): e9323. doi:10.15252/emmm.201809323. PMC   6284385 . PMID   30401727.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ↑ Rafi, Imran; Hill, Melissa; Hayward, Judith; Chitty, Lyn S (July 2017). "Non-invasive prenatal testing: use of cell-free fetal DNA in Down syndrome screening". British Journal of General Practice. 67 (660): 298–299. doi:10.3399/bjgp17X691625. PMC   5565870 . PMID   28663415.
  23. ↑ Singh, Ripudaman; Hatt, Lotte; Ravn, Katarina; Vogel, Ida; Petersen, Olav Bjørn; Uldbjerg, Niels; Schelde, Palle (September 2017). "Fetal cells in maternal blood for prenatal diagnosis: a love story rekindled". Biomarkers in Medicine. 11 (9): 705–710. doi: 10.2217/bmm-2017-0055 . PMID   28617034.
  24. ↑ Weiner, Carl P.; Lee, Gene T. (2017). "Cordocentesis". In Apuzzio, Joseph J.; Vintzileos, Anthony M.; Berghella, Vincenzo; Alvarez-Perez, Jesus R. (eds.). Operative Obstetrics, 4E. Routledge. doi:10.1201/9781315382739. ISBN   978-1-4987-2056-4.
  25. ↑ Perni, Sriram C.; Roost, John R.; Chervenak, Frank A. (2017). "Amniocentesis". In Apuzzio, Joseph J.; Vintzileos, Anthony M.; Berghella, Vincenzo; Alvarez-Perez, Jesus R. (eds.). Operative Obstetrics, 4E. Routledge. doi:10.1201/9781315382739. ISBN   978-1-4987-2056-4.
  26. ↑ Nascimento da Silva, Monica; Sicchieri, Letícia Bonfante; Rodrigues de Oliveira Silva, Flávia; Andrade, Maira Franco; Courrol, Lilia Coronato (2014). "Liquid biopsy of atherosclerosis using protoporphyrin IX as a biomarker". The Analyst. 139 (6): 1383–8. Bibcode:2014Ana...139.1383N. doi:10.1039/c3an01945d. PMID   24432352. S2CID   25707729.
  27. ↑ "What is circulating tumor DNA and how is it used to diagnose and manage cancer?: MedlinePlus Genetics". medlineplus.gov. Retrieved 2021-09-03.
  28. ↑ "What is circulating tumor DNA and how is it used to diagnose and manage cancer? ". National Institutes of Health Genetics Home Reference. 5 March 2019. Retrieved 12 March 2019.
  29. ↑ "Liquid Biopsies Show High Correlation with Tissue Biopsy for Genetic Mutations" Archived 2022-10-17 at the Wayback Machine . Oncology Practice Management. July 2016. Retrieved 12 March 2019.
  30. ↑ "Cell-free DNA as a biomarker in cancer". Extracell Vesicles Circ Nucleic Acid. Aug 2022. Retrieved 04 Aug 2022.
  31. ↑ Picher, Andy."Liquid Biopsy, Key for Precision Medicine". Genetic Engineering & Biotechnology News. 23 July 2018. Retrieved 12 March 2019.
  32. ↑ "Liquid Biopsy: Differences Among Technologies" Archived 2017-11-15 at the Wayback Machine . OncLive. 17 September 2017. Retrieved 12 March 2019.
  33. ↑ Ellis, Jen."dPCR: The Emergence of the Digital Age". Biocompare. 7 May 2018. Retrieved 12 March 2019.
  34. ↑ van der Pol Y, Mouliere F (2019). "Toward the early detection of cancer by decoding the epigenetic and environmental fingerprints of cell-free DNA". Cancer Cell. 36 (4): 350–368. doi: 10.1016/j.ccell.2019.09.003 . PMID   31614115.
  35. ↑ McDowell, Sandy."Liquid Biopsies: Past, Present, and Future". American Cancer Society. 12 February 2018. Retrieved 12 March 2019.
  36. ↑ "Liquid Biopsy: Using DNA in Blood to Detect, Track, and Treat Cancer". National Cancer Institute. 8 November 2017. Retrieved 12 March 2019.
  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. doi:10.15252/emmm.201404913. PMC   4551342 . PMID   25987569.
  38. ↑ "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". bisresearch.com. Retrieved 2022-09-19.
  39. ↑ Brito-Rocha, Tiago; Constâncio, Vera; Henrique, Rui; Jerónimo, Carmen (18 March 2023). "Shifting the Cancer Screening Paradigm: The Rising Potential of Blood-Based Multi-Cancer Early Detection Tests". Cells. 12 (6): 935. doi: 10.3390/cells12060935 . ISSN   2073-4409. PMC   10047029 . PMID   36980276.
  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. doi: 10.21037/atm.2017.01.32 . ISSN   2305-5839. PMC   5326656 . PMID   28251125.
  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. doi:10.3978/j.issn.2305-5839.2015.01.16. PMC   4356857 . PMID   25815297.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.