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Methods for the Detection of Circulating Biomarkers in Cancer Patients

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Microfluidics and Biosensors in Cancer Research

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1379))

Abstract

Liquid biopsy has emerged as one of the main pillars for personalized oncology. The term englobes body-fluid samples which contain tumor-derived material such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating extracellular vesicles (cEVs). Potential clinical application of liquid biopsy analyses includes cancer screening, detection of minimal residual disease and recurrence, therapy selection, and evaluation of acquired resistance. Despite the great developments of technology focused on circulating biomarkers characterization only cfDNA testing is nowadays implemented for the therapy selection in some advanced tumors. This can be partially explained by the fact that there is still a lack of global standardization of procedures both in the pre-analytical and analytical steps. In the present chapter, we summarize the different strategies for addressing the study of liquid biopsy taking into account their pros and cons to be applied in a clinical context and we also discuss the main technical and clinical challenges in the field of circulating biomarkers and personalized oncology.

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References

  1. Letai A (2017 Sep 8) Functional precision cancer medicine-moving beyond pure genomics. Nat Med 23(9):1028–1035

    Article  CAS  PubMed  Google Scholar 

  2. Parikh AR, Leshchiner I, Elagina L, Goyal L, Levovitz C, Siravegna G et al (2019) Liquid versus tissue biopsy for detecting acquired resistance and tumor heterogeneity in gastrointestinal cancers. Nat Med 25(9):1415–1421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Siravegna G, Marsoni S, Siena S, Bardelli A (2017 Sep) Integrating liquid biopsies into the management of cancer. Nat Rev Clin Oncol 14(9):531–548

    Article  CAS  PubMed  Google Scholar 

  4. Pantel K, Alix-Panabières C (2010 Sep) Circulating tumour cells in cancer patients: challenges and perspectives. Trends Mol Med 16(9):398–406

    Article  PubMed  Google Scholar 

  5. Leighl NB, Page RD, Raymond VM, Daniel DB, Divers SG, Reckamp KL et al (2019 Aug 1) Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res 25(15):4691–4700

    Article  CAS  PubMed  Google Scholar 

  6. André F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA et al (2021) Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol 32(2):208–217

    Article  PubMed  CAS  Google Scholar 

  7. Vidal J, Muinelo L, Dalmases A, Jones F, Edelstein D, Iglesias M et al (2017 June 1) Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients. Ann Oncol 28(6):1325–1332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. García-Foncillas J, Tabernero J, Élez E, Aranda E, Benavides M, Camps C et al (2018) Prospective multicenter real-world RAS mutation comparison between OncoBEAM-based liquid biopsy and tissue analysis in metastatic colorectal cancer. Br J Cancer 119(12):1464–1470

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Hrebien S, Citi V, Garcia-Murillas I, Cutts R, Fenwick K, Kozarewa I et al (2019) Early ctDNA dynamics as a surrogate for progression-free survival in advanced breast cancer in the BEECH trial. Ann Oncol 30(6):945–952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lee JH, Menzies AM, Carlino MS, McEvoy AC, Sandhu S, Weppler AM et al (2020) Longitudinal monitoring of ctDNA in patients with melanoma and brain metastases treated with immune checkpoint inhibitors. Clin Cancer Res 26(15):4064–4071

    Article  CAS  PubMed  Google Scholar 

  11. Moss EL, Gorsia DN, Collins A, Sandhu P, Foreman N, Gore A et al (2020 Aug 10) Utility of circulating tumor DNA for detection and monitoring of endometrial cancer recurrence and progression. Cancers 12(8):2231

    Article  CAS  PubMed Central  Google Scholar 

  12. Muinelo-Romay L, Casas-Arozamena C, Abal M (2018 Aug 7) Liquid biopsy in endometrial cancer: new opportunities for personalized oncology. Int J Mol Sci 19:2311

    Article  PubMed Central  CAS  Google Scholar 

  13. Tie J, Cohen JD, Lo SN, Wang Y, Li L, Christie M et al (2021) Prognostic significance of postsurgery circulating tumor DNA in nonmetastatic colorectal cancer: individual patient pooled analysis of three cohort studies. Int J Cancer 148(4):1014–1026

    Article  CAS  PubMed  Google Scholar 

  14. Radovich M, Jiang G, Hancock BA, Chitambar C, Nanda R, Falkson C et al (2020) Association of circulating tumor DNA and circulating tumor cells after neoadjuvant chemotherapy with disease recurrence in patients with triple-negative breast cancer: preplanned secondary analysis of the BRE12-158 randomized clinical trial. JAMA Oncol 6(9):1410–1415

    Article  PubMed  Google Scholar 

  15. Liu X, Ren J, Luo N, Guo H, Zheng Y, Li J et al (2019) Comprehensive DNA methylation analysis of tissue of origin of plasma cell-free DNA by methylated CpG tandem amplification and sequencing (MCTA-Seq). Clin Epigenetics 11(1):93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pickhardt PJ (2016) Emerging stool-based and blood-based non-invasive DNA tests for colorectal cancer screening: the importance of cancer prevention in addition to cancer detection. Abdom Radiol (New York) 41(8):1441–1444

    Article  Google Scholar 

  17. Issa IA, Noureddine M (2017 July 28) Colorectal cancer screening: an updated review of the available options. World J Gastroenterol 23(28):5086–5096

    Article  PubMed  PubMed Central  Google Scholar 

  18. Habli Z, AlChamaa W, Saab R, Kadara H, Khraiche ML (2020 Jul) Circulating tumor cell detection technologies and clinical utility: challenges and opportunities. Cancers 17:12(7)

    Google Scholar 

  19. Vasseur A, Kiavue N, Bidard F-C, Pierga J-Y, Cabel L (2021) Clinical utility of circulating tumor cells: an update. Mol Oncol 15(6):1647–1666

    Article  PubMed  CAS  Google Scholar 

  20. Zhong X, Zhang H, Zhu Y, Liang Y, Yuan Z, Li J et al (2020) Circulating tumor cells in cancer patients: developments and clinical applications for immunotherapy. Mol Cancer 19(1):15

    Article  PubMed  PubMed Central  Google Scholar 

  21. Herrero C, Abal M, Muinelo-Romay L (2020) Circulating extracellular vesicles in gynecological tumors: realities and challenges. Front Oncol 10:565666

    Article  PubMed  PubMed Central  Google Scholar 

  22. Liang Y, Lehrich BM, Zheng S, Lu M (2021) Emerging methods in biomarker identification for extracellular vesicle-based liquid biopsy. J Extracell Vesicles 10(7):e12090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Melo SA, Luecke LB, Kahlert C, Fernandez AF, Gammon ST, Kaye J et al (2015 Jul 9) Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523(7559):177–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Int Veld SGJG, Wurdinger T (2019) Tumor-educated platelets. Blood 133(22):2359–2364

    Article  CAS  Google Scholar 

  25. Griffiths JI, Wallet P, Pflieger LT, Stenehjem D, Liu X, Cosgrove PA et al (2020) Circulating immune cell phenotype dynamics reflect the strength of tumor-immune cell interactions in patients during immunotherapy. Proc Natl Acad Sci U S A 117(27):16072–16082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Allan AL, Vantyghem SA, Tuck AB, Chambers AF, Chin-Yee IH, Keeney M (2005 May) Detection and quantification of circulating tumor cells in mouse models of human breast cancer using immunomagnetic enrichment and multiparameter flow cytometry. Cytometry A 65(1):4–14

    Article  PubMed  Google Scholar 

  27. Alix-Panabières C, Pantel K (2016) Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy. Cancer Discov 6(5):479–491

    Article  PubMed  CAS  Google Scholar 

  28. Pantel K, Speicher MR (2016 Mar 10) The biology of circulating tumor cells. Oncogene 35(10):1216–1224

    Article  CAS  PubMed  Google Scholar 

  29. Alix-Panabières C, Pantel K (2013 Jan) Circulating tumor cells: liquid biopsy of cancer. Clin Chem 59(1):110–118

    Article  PubMed  CAS  Google Scholar 

  30. Riethdorf S, O’Flaherty L, Hille C, Pantel K (2018) Clinical applications of the CellSearch platform in cancer patients. Adv Drug Deliv Rev 125:102–121

    Article  CAS  PubMed  Google Scholar 

  31. Rushton AJ, Nteliopoulos G, Shaw JA, Coombes RC (2021 Feb 26) A review of circulating tumour cell enrichment technologies. Cancers 13:13(5)

    Article  CAS  Google Scholar 

  32. Hayes DF, Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Miller MC et al (2006 Jul 15) Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin Cancer Res 12(14 Pt 1):4218–4224

    Article  CAS  PubMed  Google Scholar 

  33. de Bono JS, Scher HI, Montgomery RB, Parker C, Miller MC, Tissing H et al (2008 Oct 1) Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 14(19):6302–6309

    Article  PubMed  CAS  Google Scholar 

  34. Cohen SJ, Punt CJA, Iannotti N, Saidman BH, Sabbath KD, Gabrail NY et al (2008 Jul 1) Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol 26(19):3213–3221

    Article  PubMed  Google Scholar 

  35. Grover PK, Cummins AG, Price TJ, Roberts-Thomson IC, Hardingham JE (2014 Aug) Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research. Ann Oncol 25(8):1506–1516

    Article  CAS  PubMed  Google Scholar 

  36. Kowalik A, Kowalewska M, Góźdź S (2017) Current approaches for avoiding the limitations of circulating tumor cells detection methods-implications for diagnosis and treatment of patients with solid tumors. Transl Res 185:58–84.e15

    Article  CAS  PubMed  Google Scholar 

  37. Liu Z, Fusi A, Klopocki E, Schmittel A, Tinhofer I, Nonnenmacher A et al (2011 May 19) Negative enrichment by immunomagnetic nanobeads for unbiased characterization of circulating tumor cells from peripheral blood of cancer patients. J Transl Med 9:70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Szczerba BM, Castro-Giner F, Vetter M, Krol I, Gkountela S, Landin J et al (2019) Neutrophils escort circulating tumour cells to enable cell cycle progression. Nature 566(7745):553–557

    Article  CAS  PubMed  Google Scholar 

  39. Vona G, Sabile A, Louha M, Sitruk V, Romana S, Schütze K et al (2000 Jan) Isolation by size of epithelial tumor cells: a new method for the immunomorphological and molecular characterization of circulatingtumor cells. Am J Pathol 156(1):57–63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hao S-J, Wan Y, Xia Y-Q, Zou X, Zheng S-Y (2018) Size-based separation methods of circulating tumor cells. Adv Drug Deliv Rev 125:3–20

    Article  CAS  PubMed  Google Scholar 

  41. Farace F, Massard C, Vimond N, Drusch F, Jacques N, Billiot F et al (2011 Sep 6) A direct comparison of CellSearch and ISET for circulating tumour-cell detection in patients with metastatic carcinomas. Br J Cancer 105(6):847–853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Miller MC, Robinson PS, Wagner C, O’Shannessy DJ (2018) The Parsortix™ cell separation system: a versatile liquid biopsy platform. Cytometry A 93(12):1234–1239

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hou HW, Warkiani ME, Khoo BL, Li ZR, Soo RA, Tan DS-W et al (2013) Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep 3:1259

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Gascoyne PRC, Shim S (2014 Mar 12) Isolation of circulating tumor cells by dielectrophoresis. Cancers 6(1):545–579

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L et al (2007 Dec 20) Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature 450(7173):1235–1239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Dizdar L, Fluegen G, van Dalum G, Honisch E, Neves RP, Niederacher D et al (2019) Detection of circulating tumor cells in colorectal cancer patients using the GILUPI CellCollector: results from a prospective, single-center study. Mol Oncol 13(7):1548–1558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fischer JC, Niederacher D, Topp SA, Honisch E, Schumacher S, Schmitz N et al (2013 Oct 8) Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients. Proc Natl Acad Sci U S A 110(41):16580–16585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Valihrach L, Androvic P, Kubista M (2018 Mar) Platforms for single-cell collection and analysis. Int J Mol Sci 11:19(3)

    Google Scholar 

  49. Lawson DA, Kessenbrock K, Davis RT, Pervolarakis N, Werb Z (2018) Tumour heterogeneity and metastasis at single-cell resolution. Nat Cell Biol 20(12):1349–1360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Agarwal A, Balic M, El-Ashry D, Cote RJ (2018 Mar) Circulating tumor cells. Cancer J 24(2):70–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Mondelo-Macía P, García-González J, León-Mateos L, Anido U, Aguín S, Abdulkader I et al (2021) Clinical potential of circulating free DNA and circulating tumour cells in patients with metastatic non-small-cell lung cancer treated with pembrolizumab. Mol Oncol 15(11):2923–2940

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Cortés-Hernández LE, Eslami-S Z, Pantel K, Alix-Panabières C (2020) Molecular and functional characterization of circulating tumor cells: from discovery to clinical application. Clin Chem 66(1):97–104

    Article  PubMed  Google Scholar 

  53. Sinkala E, Sollier-Christen E, Renier C, Rosàs-Canyelles E, Che J, Heirich K et al (2017) Profiling protein expression in circulating tumour cells using microfluidic western blotting. Nat Commun 8:14622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Maheswaran S, Sequist LV, Nagrath S, Ulkus L, Brannigan B, Collura CV et al (2008 Jul 24) Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 359(4):366–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Punnoose EA, Atwal S, Liu W, Raja R, Fine BM, Hughes BGM et al (2012 Apr 15) Evaluation of circulating tumor cells and circulating tumor DNA in non-small cell lung cancer: association with clinical endpoints in a phase II clinical trial of pertuzumab and erlotinib. Clin Cancer Res 18(8):2391–2401

    Article  CAS  PubMed  Google Scholar 

  56. Carter L, Rothwell DG, Mesquita B, Smowton C, Leong HS, Fernandez-Gutierrez F et al (2017) Molecular analysis of circulating tumor cells identifies distinct copy-number profiles in patients with chemosensitive and chemorefractory small-cell lung cancer. Nat Med 23(1):114–119

    Article  CAS  PubMed  Google Scholar 

  57. Krebs MG, Metcalf RL, Carter L, Brady G, Blackhall FH, Dive C (2014 Mar 21) Molecular analysis of circulating tumour cells—biology and biomarkers. Nat Rev Clin Oncol 11(3):129–144

    Article  CAS  PubMed  Google Scholar 

  58. Guo T (2016 Aug 31) Culture of circulating tumor cells - holy grail and big challenge. Int J Cancer Clin Res 3:63

    Article  Google Scholar 

  59. Pantel K, Alix-Panabières C (2019) Liquid biopsy and minimal residual disease - latest advances and implications for cure. Nat Rev Clin Oncol 16(7):409–424

    Article  CAS  PubMed  Google Scholar 

  60. Lallo A, Schenk MW, Frese KK, Blackhall F, Dive C (2017 Aug) Circulating tumor cells and CDX models as a tool for preclinical drug development. Transl Lung Cancer Res 6(4):397–408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hodgkinson CL, Morrow CJ, Li Y, Metcalf RL, Rothwell DG, Trapani F et al (2014 Aug) Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nat Med 20(8):897–903

    Article  CAS  PubMed  Google Scholar 

  62. Schölch S, García SA, Iwata N, Niemietz T, Betzler AM, Nanduri LK et al (2016 May 10) Circulating tumor cells exhibit stem cell characteristics in an orthotopic mouse model of colorectal cancer. Oncotarget 7(19):27232–27242

    Article  PubMed  PubMed Central  Google Scholar 

  63. Pereira-Veiga T, Abreu M, Robledo D, Matias-Guiu X, Santacana M, Sánchez L et al (2019) CTCs-derived xenograft development in a triple negative breast cancer case. Int J Cancer 144(9):2254–2265

    CAS  PubMed  Google Scholar 

  64. Faugeroux V, Pailler E, Oulhen M, Deas O, Brulle-Soumare L, Hervieu C et al (2020) Genetic characterization of a unique neuroendocrine transdifferentiation prostate circulating tumor cell-derived eXplant model. Nat Commun 11(1):1884

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jahr S, Hentze H, Englisch S, Hardt D, Fackelmayer FO, Hesch RD et al (2001 Feb 15) DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells. Cancer Res 61(4):1659–1665

    CAS  PubMed  Google Scholar 

  66. Kustanovich A, Schwartz R, Peretz T, Grinshpun A (2019) Life and death of circulating cell-free DNA. Cancer Biol Ther 20(8):1057–1067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Keller L, Belloum Y, Wikman H, Pantel K (2021) Clinical relevance of blood-based ctDNA analysis: mutation detection and beyond. Br J Cancer 124(2):345–358

    Article  PubMed  Google Scholar 

  68. Meddeb R, Pisareva E, Thierry AR (2019) Guidelines for the preanalytical conditions for analyzing circulating cell-free DNA. Clin Chem 65(5):623–633

    Article  CAS  PubMed  Google Scholar 

  69. van der Leest P, Boonstra PA, Ter Elst A, van Kempen LC, Tibbesma M, Koopmans J et al (2020 May 13) Comparison of circulating cell-free DNA extraction methods for downstream analysis in cancer patients. Cancers 12:1222

    Article  PubMed Central  CAS  Google Scholar 

  70. Franczak C, Filhine-Tresarrieu P, Gilson P, Merlin J-L, Au L, Harlé A (2019 Feb 1) Technical considerations for circulating tumor DNA detection in oncology. Expert Rev Mol Diagn 19(2):121–135

    Article  CAS  PubMed  Google Scholar 

  71. Mauger F, Dulary C, Daviaud C, Deleuze J-F, Tost J (2015 Sep) Comprehensive evaluation of methods to isolate, quantify, and characterize circulating cell-free DNA from small volumes of plasma. Anal Bioanal Chem 407(22):6873–6878

    Article  CAS  PubMed  Google Scholar 

  72. Kilgour E, Rothwell DG, Brady G, Dive C (2020) Liquid biopsy-based biomarkers of treatment response and resistance. Cancer Cell 37(4):485–495

    Article  CAS  PubMed  Google Scholar 

  73. Cohen JD, Li L, Wang Y, Thoburn C, Afsari B, Danilova L et al (2018 Feb 23) Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science (New York, NY). 359(6378):926–930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Abbosh C, Birkbak NJ, Swanton C (2018) Early stage NSCLC - challenges to implementing ctDNA-based screening and MRD detection. Nat Rev Clin Oncol 15(9):577–586

    Article  CAS  PubMed  Google Scholar 

  75. Wang Z, Duan J, Cai S, Han M, Dong H, Zhao J et al (2019 May 1) Assessment of blood tumor mutational burden as a potential biomarker for immunotherapy in patients with non-small cell lung cancer with use of a next-generation sequencing cancer gene panel. JAMA Oncol 5(5):696–702

    Article  PubMed  PubMed Central  Google Scholar 

  76. Martínez-Sáez O, Chic N, Pascual T, Adamo B, Vidal M, González-Farré B et al (2020) Frequency and spectrum of PIK3CA somatic mutations in breast cancer. Breast Cancer Res 22(1):45

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Malapelle U, Sirera R, Jantus-Lewintre E, Reclusa P, Calabuig-Fariñas S, Blasco A et al (2017) Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer. Expert Rev Mol Diagn 17(3):209–215

    Article  CAS  PubMed  Google Scholar 

  78. Woodhouse R, Li M, Hughes J, Delfosse D, Skoletsky J, Ma P et al (2020) Clinical and analytical validation of FoundationOne liquid CDx, a novel 324-gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin. PLoS One 15(9):e0237802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Laufer-Geva S, Rozenblum AB, Twito T, Grinberg R, Dvir A, Soussan-Gutman L et al (2018) The clinical impact of comprehensive genomic testing of circulating cell-free DNA in advanced lung cancer. J Thoracic Oncol 13(11):1705–1716

    Article  Google Scholar 

  80. Ren AH, Fiala CA, Diamandis EP, Kulasingam V (2020) Pitfalls in cancer biomarker discovery and validation with emphasis on circulating tumor DNA. Cancer Epidemiol Biomarker Prev 29(12):2568–2574

    Article  CAS  Google Scholar 

  81. Elazezy M, Joosse SA (2018) Techniques of using circulating tumor DNA as a liquid biopsy component in cancer management. Comput Struct Biotechnol J 16:370–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Bando H, Kagawa Y, Kato T, Akagi K, Denda T, Nishina T et al (2019) A multicentre, prospective study of plasma circulating tumour DNA test for detecting RAS mutation in patients with metastatic colorectal cancer. Br J Cancer 120(10):982–986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chen M, Zhao H (2019) Next-generation sequencing in liquid biopsy: cancer screening and early detection. Hum Genomics 13(1):34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Szilágyi M, Pös O, Márton É, Buglyó G, Soltész B, Keserű J et al (2020 Sep 17) Circulating cell-free nucleic acids: main characteristics and clinical application. Int J Mol Sci 21:6827

    Article  PubMed Central  CAS  Google Scholar 

  85. Rodriguez-Casanova A, Costa-Fraga N, Bao-Caamano A, López-López R, Muinelo-Romay L, Diaz-Lagares A (2021) Epigenetic landscape of liquid biopsy in colorectal cancer. Front Cell Dev Biol 9:622459

    Article  PubMed  PubMed Central  Google Scholar 

  86. Portela A, Esteller M (2010 Oct) Epigenetic modifications and human disease. Nat Biotechnol 28(10):1057–1068

    Article  CAS  PubMed  Google Scholar 

  87. Huang J, Wang L (2019 Nov) Cell-free DNA methylation profiling analysis-technologies and bioinformatics. Cancers 6:11(11)

    Google Scholar 

  88. Frommer M, McDonald LE, Millar DS, Collis CM, Watt F, Grigg GW et al (1992 Mar 1) A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc Natl Acad Sci U S A 89(5):1827–1831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Li M, Chen W-D, Papadopoulos N, Goodman SN, Bjerregaard NC, Laurberg S et al (2009 Sep) Sensitive digital quantification of DNA methylation in clinical samples. Nat Biotechnol 27(9):858–863

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Chimonidou M, Strati A, Tzitzira A, Sotiropoulou G, Malamos N, Georgoulias V et al (2011 Aug) DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells. Clin Chem 57(8):1169–1177

    Article  CAS  PubMed  Google Scholar 

  91. Boeckx N, Op de Beeck K, Beyens M, Deschoolmeester V, Hermans C, De Clercq P et al (2018) Mutation and methylation analysis of circulating tumor DNA can be used for follow-up of metastatic colorectal cancer patients. Clin Colorectal Cancer 17(2):e369–e379

    Article  PubMed  Google Scholar 

  92. Barault L, Amatu A, Bleeker FE, Moutinho C, Falcomatà C, Fiano V et al (2015 Sep) Digital PCR quantification of MGMT methylation refines prediction of clinical benefit from alkylating agents in glioblastoma and metastatic colorectal cancer. Ann Oncol 26(9):1994–1999

    Article  CAS  PubMed  Google Scholar 

  93. Gallardo-Gómez M, Moran S, Páez de la Cadena M, Martínez-Zorzano VS, Rodríguez-Berrocal FJ, Rodríguez-Girondo M et al (2018) A new approach to epigenome-wide discovery of non-invasive methylation biomarkers for colorectal cancer screening in circulating cell-free DNA using pooled samples. Clin Epigenetics 10:53

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Friedlander TW, Ngo VT, Dong H, Premasekharan G, Weinberg V, Doty S et al (2014 May 15) Detection and characterization of invasive circulating tumor cells derived from men with metastatic castration-resistant prostate cancer. Int J Cancer 134(10):2284–2293

    Article  CAS  PubMed  Google Scholar 

  95. Li W, Li Q, Kang S, Same M, Zhou Y, Sun C et al (2018) CancerDetector: ultrasensitive and non-invasive cancer detection at the resolution of individual reads using cell-free DNA methylation sequencing data. Nucleic Acids Res 46(15):e89

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Gkountela S, Castro-Giner F, Szczerba BM, Vetter M, Landin J, Scherrer R et al (2019) Circulating tumor cell clustering shapes dna methylation to enable metastasis seeding. Cell. 176(1–2):98–112.e14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Raposo G, Stoorvogel W (2013 Feb 18) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200(4):373–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. György B, Szabó TG, Pásztói M, Pál Z, Misják P, Aradi B et al (2011 Aug) Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci 68(16):2667–2688

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Colombo M, Raposo G, Théry C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289

    Article  CAS  PubMed  Google Scholar 

  100. Théry C, Ostrowski M, Segura E (2009 Aug) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9(8):581–593

    Article  PubMed  CAS  Google Scholar 

  101. van der Meel R, Krawczyk-Durka M, van Solinge WW, Schiffelers RM (2014 Jun) Toward routine detection of extracellular vesicles in clinical samples. Int J Lab Hematol 36(3):244–253

    Article  PubMed  Google Scholar 

  102. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ et al (1996 Mar 1) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183(3):1161–1172

    Article  CAS  PubMed  Google Scholar 

  103. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D et al (1998 May) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4(5):594–600

    Article  CAS  PubMed  Google Scholar 

  104. Yáñez-Mó M, Siljander PR-M, Andreu Z, Zavec AB, Borràs FE, Buzas EI et al (2015) Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles 4:27066

    Article  PubMed  Google Scholar 

  105. Kalluri R (2016 Apr 1) The biology and function of exosomes in cancer. J Clin Invest 126(4):1208–1215

    Article  PubMed  PubMed Central  Google Scholar 

  106. Akers JC, Gonda D, Kim R, Carter BS, Chen CC (2013 May) Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neuro-Oncol 113(1):1–11

    Article  Google Scholar 

  107. Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P et al (2006 May) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20(5):847–856

    Article  CAS  PubMed  Google Scholar 

  108. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO (2007 Jun) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659

    Article  CAS  PubMed  Google Scholar 

  109. Lai RC, Yeo RWY, Tan KH, Lim SK (2013) Exosomes for drug delivery: a novel application for the mesenchymal stem cell. Biotechnol Adv. 31(5):543–551

    Article  CAS  PubMed  Google Scholar 

  110. Zaborowski MP, Balaj L, Breakefield XO, Lai CP (2015 Aug 1) Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience 65(8):783–797

    Article  PubMed  PubMed Central  Google Scholar 

  111. Hood JL, San RS, Wickline SA (2011 Jun 1) Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res 71(11):3792–3801

    Article  CAS  PubMed  Google Scholar 

  112. Rak J (2010 Nov) Microparticles in cancer. Semin Thromb Hemost 36(8):888–906

    Article  CAS  PubMed  Google Scholar 

  113. Cocucci E, Racchetti G, Meldolesi J (2009 Feb) Shedding microvesicles: artefacts no more. Trends Cell Biol 19(2):43–51

    Article  CAS  PubMed  Google Scholar 

  114. Zhang H-G, Grizzle WE (2011 Mar 1) Exosomes and cancer: a newly described pathway of immune suppression. Clin Cancer Res 17(5):959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Logozzi M, de Milito A, Lugini L, Borghi M, Calabrò L, Spada M et al (2009 Apr 17) High levels of exosomes expressing CD63 and Caveolin-1 in plasma of melanoma patients. PLoS One 4(4):e5219

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Ciardiello C, Cavallini L, Spinelli C, Yang J, Reis-Sobreiro M, de Candia P et al (2016 Feb 6) Focus on extracellular vesicles: new Frontiers of cell-to-cell communication in cancer. Int J Mol Sci 17(2):175

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Carvalho J, Oliveira C (2014) Extracellular vesicles - powerful markers of cancer EVolution. Front Immunol 5:685

    PubMed  Google Scholar 

  118. Nosova VP, Alekseeva LM, Bobkov II, Mumladze RB, Popova OA (1989) Changes in the rheologic properties of the blood in peptic ulcer. Sov Med. 4:87–90

    Google Scholar 

  119. Théry C, Zitvogel L, Amigorena S (2002 Aug) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2(8):569–579

    Article  PubMed  CAS  Google Scholar 

  120. Kahlert C, Kalluri R (2013 Apr) Exosomes in tumor microenvironment influence cancer progression and metastasis. J Mol Med (Berlin, Germany) 91(4):431–437

    Article  CAS  Google Scholar 

  121. van Niel G, D’Angelo G, Raposo G (2018) Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol 19(4):213–228

    Article  PubMed  CAS  Google Scholar 

  122. Doyle LM, Wang MZ (2019) Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells 8(7):727

    Article  CAS  PubMed Central  Google Scholar 

  123. Herrero C, de la Fuente A, Casas-Arozamena C, Sebastian V, Prieto M, Arruebo M et al (2019 Dec 12) Extracellular vesicles-based biomarkers represent a promising liquid biopsy in endometrial cancer. Cancers 11:2000

    Article  CAS  PubMed Central  Google Scholar 

  124. Mathai RA, Vidya RVS, Reddy BS, Thomas L, Udupa K, Kolesar J et al (2019 Mar) Potential utility of liquid biopsy as a diagnostic and prognostic tool for the assessment of solid tumors: implications in the precision oncology. J Clin Med 18:8(3)

    Google Scholar 

  125. Lötvall J, Hill AF, Hochberg F, Buzás EI, di Vizio D, Gardiner C et al (2014) Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 3:26913

    Article  PubMed  Google Scholar 

  126. Théry C, Amigorena S, Raposo G, Clayton A (2006 Apr) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chapter 3:Unit 3.22

    PubMed  Google Scholar 

  127. Hiemstra TF, Charles PD, Gracia T, Hester SS, Gatto L, Al-Lamki R et al (2014 Sep) Human urinary exosomes as innate immune effectors. J Am Soc Nephrol 25(9):2017–2027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Zarovni N, Corrado A, Guazzi P, Zocco D, Lari E, Radano G et al (2015 Oct 1) Integrated isolation and quantitative analysis of exosome shuttled proteins and nucleic acids using immunocapture approaches. Methods (San Diego, Calif). 87:46–58

    Article  CAS  Google Scholar 

  129. Gardiner C, di Vizio D, Sahoo S, Théry C, Witwer KW, Wauben M et al (2016) Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. J Extracell Vesicles 5:32945

    Article  PubMed  CAS  Google Scholar 

  130. Momen-Heravi F, Balaj L, Alian S, Mantel P-Y, Halleck AE, Trachtenberg AJ et al (2013 Oct) Current methods for the isolation of extracellular vesicles. Biol Chem 394(10):1253–1262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Livshits MA, Livshts MA, Khomyakova E, Evtushenko EG, Lazarev VN, Kulemin NA et al (2015 Nov 30) Isolation of exosomes by differential centrifugation: theoretical analysis of a commonly used protocol. Sci Rep 5:17319

    Article  PubMed  CAS  Google Scholar 

  132. Webber J, Clayton A (2013) How pure are your vesicles? J Extracell Vesicles 2

    Google Scholar 

  133. van Deun J, Mestdagh P, Sormunen R, Cocquyt V, Vermaelen K, Vandesompele J et al (2014) The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J Extracell Vesicles 3

    Google Scholar 

  134. Li P, Kaslan M, Lee SH, Yao J, Gao Z (2017) Progress in exosome isolation techniques. Theranostics 7(3):789–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B et al (2016 Feb 23) Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci U S A 113(8):E968–E977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Shao H, Im H, Castro CM, Breakefield X, Weissleder R, Lee H (2018) New technologies for analysis of extracellular vesicles. Chem Rev 118(4):1917–1950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Tauro BJ, Greening DW, Mathias RA, Ji H, Mathivanan S, Scott AM et al (2012 Feb) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods (San Diego, Calif). 56(2):293–304

    Article  CAS  Google Scholar 

  138. Zhang M, Jin K, Gao L, Zhang Z, Li F, Zhou F et al (2018 Sep) Methods and technologies for exosome isolation and characterization. Small Methods 2(9):1800021

    Article  CAS  Google Scholar 

  139. Zeringer E, Barta T, Li M, Vlassov A (2015 Apr 1) v. Strategies for isolation of exosomes. Cold Spring Harb Protoc 2015(4):319–323

    Article  PubMed  Google Scholar 

  140. Liga A, Vliegenthart ADB, Oosthuyzen W, Dear JW, Kersaudy-Kerhoas M (2015 Jun 7) Exosome isolation: a microfluidic road-map. Lab Chip 15(11):2388–2394

    Article  CAS  PubMed  Google Scholar 

  141. Batrakova EV, Kim MS (2015 Dec 10) Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. 219:396–405

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Grubisic Z, Rempp P, Benoit H (1967 Sep) A universal calibration for gel permeation chromatography. J Polym Sci B Polym Lett 5(9):753–759

    Article  Google Scholar 

  143. Feng Y, Huang W, Wani M, Yu X, Ashraf M (2014) Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22. PLoS One 9(2):e88685

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  144. Roura S, Gámez-Valero A, Lupón J, Gálvez-Montón C, Borràs FE, Bayes-Genis A (2018) Proteomic signature of circulating extracellular vesicles in dilated cardiomyopathy. Lab Investig. 98(10):1291–1299

    Article  CAS  PubMed  Google Scholar 

  145. Gámez-Valero A, Monguió-Tortajada M, Carreras-Planella L, Franquesa M, Beyer K, Borràs FE (2016) Size-exclusion chromatography-based isolation minimally alters extracellular vesicles’ characteristics compared to precipitating agents. Sci Rep 6:33641

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Musante L, Tataruch D, Gu D, Benito-Martin A, Calzaferri G, Aherne S et al (2014 Dec 23) A simplified method to recover urinary vesicles for clinical applications, and sample banking. Sci Rep 4:7532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Samsonov R, Shtam T, Burdakov V, Glotov A, Tsyrlina E, Berstein L et al (2016 Jan) Lectin-induced agglutination method of urinary exosomes isolation followed by mi-RNA analysis: application for prostate cancer diagnostic. Prostate 76(1):68–79

    Article  CAS  PubMed  Google Scholar 

  148. Hu JL, Wang W, Lan XL, Zeng ZC, Liang YS, Yan YR et al (2019) CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer. Mol Cancer 18(1):91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Małys MSS, Aigner C, Schulz SMM, Schachner H, Rees AJJ, Kain R (2021 Apr 28) Isolation of small extracellular vesicles from human sera. Int J Mol Sci 22(9):4653

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Konoshenko MY, Lekchnov EA, Vlassov AV, Laktionov PP (2018) Isolation of extracellular vesicles: general methodologies and latest trends. BioMed Res Int. 2018:8545347

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  151. Huang T, Song C, Zheng L, Xia L, Li Y, Zhou Y (2019) The roles of extracellular vesicles in gastric cancer development, microenvironment, anti-cancer drug resistance, and therapy. Mol Cancer 18(1):62

    Article  PubMed  PubMed Central  Google Scholar 

  152. Nolte-‘t Hoen ENM, Buermans HPJ, Waasdorp M, Stoorvogel W, Wauben MHM, ‘t Hoen PAC (2012 Oct) Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res 40(18):9272–9285

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  153. Kim KM, Abdelmohsen K, Mustapic M, Kapogiannis D, Gorospe M (2017) RNA in extracellular vesicles. Wiley Interdiscip Rev RNA 8(4):10.1002/wrna.1413

    Article  PubMed Central  CAS  Google Scholar 

  154. Elzanowska J, Semira C, Costa-Silva B (2021) DNA in extracellular vesicles: biological and clinical aspects. Mol Oncol 15(6):1701–1714

    Article  PubMed  CAS  Google Scholar 

  155. Kahlert C, Melo SA, Protopopov A, Tang J, Seth S, Koch M et al (2014 Feb 14) Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem 289(7):3869–3875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B et al (2014 Jun) Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 24(6):766–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Ricklefs FL, Alayo Q, Krenzlin H, Mahmoud AB, Speranza MC, Nakashima H et al (2018) Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv. 4(3):eaar2766

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Wu F, Gu Y, Kang B, Heskia F, Pachot A, Bonneville M et al (2021 Jun) PD-L1 detection on circulating tumor-derived extracellular vesicles (T-EVs) from patients with lung cancer. Transl Lung Cancer Res 10(6):2441–2451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Nilsson RJA, Balaj L, Hulleman E, van Rijn S, Pegtel DM, Walraven M et al (2011 Sep 29) Blood platelets contain tumor-derived RNA biomarkers. Blood 118(13):3680–3683

    Article  PubMed  PubMed Central  Google Scholar 

  160. Luo C-L, Xu Z-G, Chen H, Ji J, Wang Y-H, Hu W et al (2018) LncRNAs and EGFRvIII sequestered in TEPs enable blood-based NSCLC diagnosis. Cancer Manag Res 10:1449–1459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Best MG, Vancura A, Wurdinger T (2017) Platelet RNA as a circulating biomarker trove for cancer diagnostics. J Thromb Haemost 15(7):1295–1306

    Article  CAS  PubMed  Google Scholar 

  162. Park C-K, Kim J-E, Kim M-S, Kho B-G, Park H-Y, Kim T-O et al (2019 Aug) Feasibility of liquid biopsy using plasma and platelets for detection of anaplastic lymphoma kinase rearrangements in non-small cell lung cancer. J Cancer Res Clin Oncol 145(8):2071–2082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Roweth HG, Battinelli EM (2021) Lessons to learn from tumor-educated platelets. Blood 137(23):3174–3180

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Klement GL, Yip T-T, Cassiola F, Kikuchi L, Cervi D, Podust V et al (2009 Mar 19) Platelets actively sequester angiogenesis regulators. Blood 113(12):2835–2842

    Article  CAS  PubMed  Google Scholar 

  165. Jiang T, Bai Y, Zhou F, Li W, Gao G, Su C et al (2019) Clinical value of neutrophil-to-lymphocyte ratio in patients with non-small-cell lung cancer treated with PD-1/PD-L1 inhibitors. Lung Cancer (Amsterdam, Netherlands) 130:76–83

    Article  Google Scholar 

  166. Bryant AK, Sankar K, Strohbehn GW, Zhao L, Elliott D, Qin A et al (2022) Prognostic and predictive value of neutrophil-to-lymphocyte ratio with adjuvant immunotherapy in stage III non-small-cell lung cancer. Lung Cancer (Amsterdam, Netherlands) 163:35–41

    Article  Google Scholar 

  167. Gibney GT, Weiner LM, Atkins MB (2016 Dec) Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 17(12):e542–e551

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Kim CG, Hong MH, Kim KH, Seo I-H, Ahn B-C, Pyo K-H et al (2021 Jan) Dynamic changes in circulating PD-1+ CD8+ T lymphocytes for predicting treatment response to PD-1 blockade in patients with non-small-cell lung cancer. Eur J Cancer 143:113–126

    Article  CAS  PubMed  Google Scholar 

  169. Capone M, Fratangelo F, Giannarelli D, Sorrentino C, Turiello R, Zanotta S et al (2020) Frequency of circulating CD8+CD73+T cells is associated with survival in nivolumab-treated melanoma patients. J Transl Med 18(1):121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Meyer C, Cagnon L, Costa-Nunes CM, Baumgaertner P, Montandon N, Leyvraz L et al (2014 Mar) Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol Immunother 63(3):247–257

    Article  CAS  PubMed  Google Scholar 

  171. De Mattos-Arruda L, Siravegna G (2021) How to use liquid biopsies to treat patients with cancer. ESMO Open 6(2):100060

    Article  PubMed  PubMed Central  Google Scholar 

  172. Gerber T, Taschner-Mandl S, Saloberger-Sindhöringer L, Popitsch N, Heitzer E, Witt V et al (2020) Assessment of pre-analytical sample handling conditions for comprehensive liquid biopsy analysis. J Mol Diagn 22(8):1070–1086

    Article  CAS  PubMed  Google Scholar 

  173. Fleischhacker M, Schmidt B (2020 Jun 25) Pre-analytical issues in liquid biopsy – where do we stand? J Lab Med 44(3):117–142

    Article  Google Scholar 

  174. Hu Y, Ulrich BC, Supplee J, Kuang Y, Lizotte PH, Feeney NB et al (2018) False-positive plasma genotyping due to clonal hematopoiesis. Clin Cancer Res 24(18):4437–4443

    Article  CAS  PubMed  Google Scholar 

  175. YMD L, DSC H, Jiang P, RWK C (2021 Apr 9) Epigenetics, fragmentomics, and topology of cell-free DNA in liquid biopsies. Science 372(6538):eaaw3616

    Article  CAS  Google Scholar 

  176. Ayers L, Pink R, Carter DRF, Nieuwland R (2019) Clinical requirements for extracellular vesicle assays. J Extracell Vesicles 8(1):1593755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Translational Medical Oncology Group (Oncomet), Health Research Foundation Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain

    Patricia Mondelo-Macía, Ana María Rodríguez-Ces, María Mercedes Suárez-Cunqueiro & Laura Muinelo Romay

  2. Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain

    Patricia Mondelo-Macía & Ana María Rodríguez-Ces

  3. Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain

    Patricia Mondelo-Macía, Ana María Rodríguez-Ces, María Mercedes Suárez-Cunqueiro & Laura Muinelo Romay

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  1. Patricia Mondelo-Macía
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  2. Ana María Rodríguez-Ces
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  3. María Mercedes Suárez-Cunqueiro
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  1. 3B’s Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics at the University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal

    David Caballero

  2. 3B’s Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics at the University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Subhas C. Kundu

  3. 3B’s Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics at the University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimarães, Portugal

    Rui L. Reis

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Mondelo-Macía, P., Rodríguez-Ces, A.M., Suárez-Cunqueiro, M.M., Romay, L.M. (2022). Methods for the Detection of Circulating Biomarkers in Cancer Patients. In: Caballero, D., Kundu, S.C., Reis, R.L. (eds) Microfluidics and Biosensors in Cancer Research. Advances in Experimental Medicine and Biology, vol 1379. Springer, Cham. https://doi.org/10.1007/978-3-031-04039-9_21

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