Circulating microRNAs and liquid biopsy: murine xenograft models for technical validation of clinical protocols

Abstract

In oncology, liquid biopsy is applied to detect with high efficiency clinically relevant analytes, such as tumor cells, cell-free nucleic acids, and exosomes in peripheral blood and other body fluids of cancer patients. Liquid biopsy is considered one of the most advanced non-invasive diagnostic systems useful, in the next future, for enabling personalized treatments in precision medicine. Medical actions include, but are not limited to, early diagnosis, staging, prognosis, anticipation (lead time) and prediction of therapy responses, as well as follow up. Experimental system for validation of the proposed liquid biopsy approaches is highly needed. In this review article we will discuss the establishment of xenotransplanted mouse model systems for the validation of liquid biopsy protocols aimed to identify changes in the miRNA plasma content. Human colon cancer HT-29 and LoVo cells have been xenotransplanted and miR-221-3p and miR-222-3p have been comparatively analyzed in cultured HT-29 and LoVo cells, xenotransplants and plasma samples.

Keywords

Liquid biopsy / circulating tumor RNA / microRNA / xenograft

References

[1] Heitzer E,Ulz P,Speicher MR.Circulating tumor cells and DNA as liquid biopsies..Genome Med2013;5:73 PMCID:PMC3979149

[2] Bettegowda C,Leary RJ,Wang Y.Detection of circulating tumor DNA in early- and late-stage human malignancies..Sci Transl Med2014;6:224ra24 PMCID:PMC4017867

[3] Newman AM,To J,Eclov NC.An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage..Nat Med2014;20:548-54 PMCID:PMC4016134

[4] Breitbach S,Helmig S,Kubiak T.Direct quantification of cell-free, circulating DNA from unpurified plasma..PLoS One2014;9:e87838 PMCID:PMC3940427

[5] Heitzer E,Geigl JB.Circulating tumor DNA as a liquid biopsy for cancer..Clin Chem2015;61:112-23

[6] Diehl F,Choti MA,Goodman S.Circulating mutant DNA to assess tumor dynamics..Nat Med2008;14:985-90 PMCID:PMC2820391

[7] Leon SA,Sklaroff DM.Free DNA in the serum of cancer patients and the effect of therapy..Cancer Res1977;37:646-50

[8] Sozzi G,Mariani L,Roz L.Analysis of circulating tumor DNA in plasma at diagnosis and during follow-up of lung cancer patients..Cancer Res2001;61:4675-8

[9] Spindler KL,Vogelius I.Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan..Clin Cancer Res2012;18:1177-85

[10] Perkins G,Pope L,Dukes JP.Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers..PLoS One2012;7:e47020 PMCID:PMC3492590

[11] Ignatiadis M,Jeffrey SS.Circulating tumor cells and circulating tumor DNA: challenges and opportunities on the path to clinical utility..Clin Cancer Res2015;21:4786-800

[12] Krebs MG,Ward TH,Dive C.Circulating tumour cells: their utility in cancer management and predicting outcomes..Ther Adv Med Oncol2010;2:351-65 PMCID:PMC3126032

[13] Millner LM,Valdes R.Circulating tumor cells: a review of present methods and the need to identify heterogeneous phenotypes..Ann Clin Lab Sci2013;43:295-304 PMCID:PMC5060940

[14] Kuipers EJ.Personalized screening for colorectal cancer..Nat Rev Gastroenterol Hepatol2018;15:391-2

[15] Hardingham JE,Winter M,Price TJ.Detection and clinical significance of circulating tumor cells in colorectal cancer-20 years of progress..Mol Med.2015;21 Suppl 1:S25-31 PMCID:PMC4661051

[16] Kloten V,Brüchle NO,Freudenmacher N.Liquid biopsy in colon cancer: comparison of different circulating DNA extraction systems following absolute quantification of KRAS mutations using Intplex allele-specific PCR..Oncotarget2017;8:86253-63 PMCID:PMC5689682

[17] Thomsen CEB,Andersen RF,Jensen LH.The prognostic value of simultaneous tumor and serum RAS/RAF mutations in localized colon cancer..Cancer Med2017;6:928-36 PMCID:PMC5430097

[18] Veldore VH,Routhu T,Noronha V.Validation of liquid biopsy: plasma cell-free DNA testing in clinical management of advanced non- small cell lung cancer..Lung Cancer (Auckl)2018;9:1-11 PMCID:PMC5757203

[19] Anfossi S,Pantel K.Clinical utility of circulating non-coding RNAs - an update..Nat Rev Clin Oncol2018;15:541-63

[20] Izzotti A,Pulliero A,Ravetti JL.Extracellular microRNA in liquid biopsy: applicability in cancer diagnosis and prevention..Am J Cancer Res2016;6:1461-93 PMCID:PMC4969398

[21] Huang Z,Ni S,Sheng W.Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer..Int J Cancer2010;127:118-26

[22] Ogata-Kawata H,Kurioka D,Yamada Y.Circulating exosomal microRNAs as biomarkers of colon cancer..PLoS One2014;9:e92921 PMCID:PMC3976275

[23] Ng EK,Jin H,Shin VY.Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening..Gut2009;58:1375-81

[24] Zheng G,Yang X,Wang L.Serum microRNA panel as biomarkers for early diagnosis of colorectal adenocarcinoma..Br J Cancer2014;111:1985-92 PMCID:PMC4229633

[25] Ghelani HS,Gokani RH.MicroRNAs as newer therapeutic targets: a big hope from a tiny player..J Pharmacol Pharmacother2012;3:217-27 PMCID:PMC3487269

[26] Krol J,Filipowicz W.The widespread regulation of microRNA biogenesis, function and decay..Nat Rev Genet2010;11:597-610

[27] Gambari R,Borgatti M,Finotti A.Targeting microRNAs involved in human diseases: a novel approach for modification of gene expression and drug development..Biochem Pharmacol2011;82:1416-29

[28] Piva R,Gambari R.From microRNA functions to microRNA therapeutics: novel targets and novel drugs in breast cancer research and treatment..Int J Oncol2013;43:985-94 PMCID:PMC3829774

[29] Gambari R,Spandidos DA.Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: Νew trends in the development of miRNA therapeutic strategies in oncology..Int J Oncol2016;49:5-32 PMCID:PMC4902075

[30] Nishida-Aoki N.Interactions between cancer cells and normal cells via miRNAs in extracellular vesicles..Cell Mol Life Sci2015;72:1849-61 PMCID:PMC4412282

[31] Schetter AJ,Harris CC.The role of microRNAs in colorectal cancer..Cancer J2012;18:244-52 PMCID:PMC3397427

[32] Gheinani AH,Baumgartner U,Draeger A.Improved isolation strategies to increase the yield and purity of human urinary exosomes for biomarker discovery..Sci Rep2018;8:3945 PMCID:PMC5834546

[33] da Silveira JC,Del Collado M,Sangalli JR.Supplementation with small-extracellular vesicles from ovarian follicular fluid during in vitro production modulates bovine embryo development..PLoS One2017;12:e0179451 PMCID:PMC5472319

[34] Halvorsen AR,Gromov P,Talman MM.Profiling of microRNAs in tumor interstitial fluid of breast tumors - a novel resource to identify biomarkers for prognostic classification and detection of cancer..Mol Oncol2017;11:220-34 PMCID:PMC5527454

[35] Valentino A,Sirera R,Camps C.Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer..Clin Transl Oncol2017;19:651-7

[36] Wecker T,Plötner A,Horres R.MicroRNA Profiling in Aqueous Humor of Individual Human Eyes by Next-Generation Sequencing..Invest Ophthalmol Vis Sci2016;57:1706-13

[37] Pu XX,Guo HQ,Li H.Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression..J Gastroenterol Hepatol2010;25:1674-80

[38] Liu GH,Chen R,Zhou B.Serum miR-21 and miR-92a as biomarkers in the diagnosis and prognosis of colorectal cancer..Tumour Biol2013;34:2175-81

[39] Cheng H,Cogdell DE,Schetter AJ.Circulating plasma MiR- 141 is a novel biomarker for metastatic colon cancer and predicts poor prognosis..PLoS One2011;6:e17745 PMCID:PMC3060165

[40] Lv ZC,Chen HB.Investigation of microRNA-155 as a serum diagnostic and prognostic biomarker for colorectal cancer..Tumour Biol2015;36:1619-25

[41] Krawczyk P,Olesiński T,Dziwota J.Evaluation of miR-506 and miR-4316 expression in early and non-invasive diagnosis of colorectal cancer..Int J Colorectal Dis2017;32:1057-60 PMCID:PMC5486640

[42] Liu C,Shen J,Takata Y.Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer..Oncotarget2016;7:76250-60 PMCID:PMC5342811

[43] Li N,Guarnera MA,Cai L.Digital PCR quantification of miRNAs in sputum for diagnosis of lung cancer..J Cancer Res Clin Oncol2014;140:145-50 PMCID:PMC3898839

[44] Leng Q,Jiang F,Zhan M.A plasma miRNA signature for lung cancer early detection..Oncotarget2017;8:111902-11 PMCID:PMC5762367

[45] Margue C,Philippidou D,Walters C.Comparison of a healthy miRNome with melanoma patient miRNomes: are microRNAs suitable serum biomarkers for cancer?.Oncotarget2015;6:12110-27 PMCID:PMC4494926

[46] Müllauer L.Next generation sequencing: clinical applications in solid tumours..Memo2017;10:244-7 PMCID:PMC5725522

[47] Giuffrida MC,D'Agata R,Gambari R.Isothermal circular- strand-displacement polymerization of DNA and microRNA in digital microfluidic devices..Anal Bioanal Chem2015;407:1533-43

[48] Guo Q,Wang K,Li W.Sensitive fluorescence detection of nucleic acids based on isothermal circular strand-displacement polymerization reaction..Nucleic Acids Res2009;37:e20 PMCID:PMC2647313

[49] D'Agata R,Zanoli LM,Spoto G.Direct detection of point mutations in nonamplified human genomic DNA..Anal Chem2011;83:8711-7

[50] Bellassai N.Biosensors for liquid biopsy: circulating nucleic acids to diagnose and treat cancer..Anal Bioanal Chem2016;408:7255-64

[51] Finotti A,Gasparello J,Spandidos DA.Liquid biopsy and PCR-free ultrasensitive detection systems in oncology..Int J Oncol2018;53:1395-1434 PMCID:PMC6086621

[52] Mitchell PS,Kroh EM,Wyman SK.Circulating microRNAs as stable blood-based markers for cancer detection..Proc Natl Acad Sci U S A2008;105:10513-8 PMCID:PMC2492472

[53] Hu Z,Zhao Y,Jin G.Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer..J Clin Oncol2010;28:1721-6

[54] Selth LA,Gillis JL,Murti K.Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease..Int J Cancer2012;131:652-61

[55] Gasparello J,Tremante E,Amoreo CA.Liquid biopsy in mice bearing colorectal carcinoma xenografts: gateways regulating the levels of circulating tumor DNA (ctDNA) and miRNA (ctmiRNA)..J Exp Clin Cancer Res2018;37:124 PMCID:PMC6020232

[56] Greystoke A,Rothwell DG,Burt D.Development of a circulating miRNA assay to monitor tumor burden: From mouse to man..Mol Oncol2016;10:282-91 PMCID:PMC4750526

[57] Chapin SC.Ultrasensitive multiplexed microRNA quantification on encoded gel microparticles using rolling circle amplification..Anal Chem2011;83:7179-85 PMCID:PMC3173568

[58] Williams MR,Stedtfeld TM,Hashsham SA.Quantification of microRNAs directly from body fluids using a base-stacking isothermal amplification method in a point-of-care device..Biomed Microdevices2017;19:45 PMCID:PMC5896010

[59] Valoczi A,Varga N,Kauppinen S.Sensitive and specific detection of microRNAs by northern blot analysis using LNA-modified oligonucleotide probes..Nucleic Acids Res2004;32:e175 PMCID:PMC545470

[60] Lu J,Miska EA,Lamb J.MicroRNA expression profiles classify human cancers..Nature2005;435:834-8

[61] Garcia-Olmo DC,Ruiz-Piqueras R,Garcia-Olmo D.Detection of circulating tumor cells and of tumor DNA in plasma during tumor progression in rats..Cancer Lett2005;217:115-23

[62] Rago C,Diehl F,Liu G.Serial assessment of human tumor burdens in mice by the analysis of circulating DNA..Cancer Res2007;67:9364-70

[63] Thierry AR,Gongora C,Robert B.Origin and quantification of circulating DNA in mice with human colorectal cancer xenografts..Nucleic Acids Res2010;38:6159-75 PMCID:PMC2952865

[64] Goodale D,Postenka CO,Allan AL.Characterization of tumor cell dissemination patterns in preclinical models of cancer metastasis using flow cytometry and laser scanning cytometry..Cytometry A2009;75A:344-55

[65] Fan ZC,Liu GD,Weng XF.Real-time monitoring of rare circulating hepatocellular carcinoma cells in an orthotopic model by in vivo flow cytometry assesses resection on metastasis..Cancer Res2012;72:2683-91

[66] Welch DR.Technical considerations for studying cancer metastasis in vivo..Clin Exp Metastasis1997;15:272-306

[67] Kersten K,van Miltenburg MH.Genetically engineered mouse models in oncology research and cancer medicine..EMBO Mol Med2017;9:137-53 PMCID:PMC5286388

[68] Gengenbacher N,Augustin HG.Preclinical mouse solid tumour models: status quo, challenges and perspectives..Nat Rev Cancer2017;17:751-65

[69] Giuliano M,Christiny P,Creighton CJ.Circulating and disseminated tumor cells from breast cancer patient-derived xenograft-bearing mice as a novel model to study metastasis..Breast Cancer Res2015;17:3 PMCID:PMC4318479

[70] Waters PS,Wall D,Miller N.Relationship between circulating and tissue microRNAs in a murine model of breast cancer..PLoS One2012;7:e50459 PMCID:PMC3511577

[71] Zhang G,Li B,Chu C.MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer..Breast Cancer Res2017;19:73 PMCID:PMC5480201

[72] Zhou ZP,Hong ZS,Wang MZ.Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways..Int J Oncol2018;53:1183-92

[73] Bai B,Zhang R,Jiang Y.Dual-agonist occupancy of orexin receptor 1 and cholecystokinin A receptor heterodimers decreases G-protein-dependent signaling and migration in the human colon cancer cell line HT-29..Biochim Biophys Acta Mol Cell Res2017;1864:1153-64

[74] Maeda K,Qi Y.In vitro and in vivo induction of human LoVo cells into apoptotic process by non-invasive microwave treatment: a potentially novel approach for physical therapy of human colorectal cancer..Oncol Rep2004;11:771-5

[75] Qin J.MicroRNA-221 promotes colorectal cancer cell invasion and metastasis by targeting RECK..FEBS Lett2014;588:99-104

[76] Xu K,Shen K,Cui D.MiR-222 modulates multidrug resistance in human colorectal carcinoma by down-regulating ADAM-17..Exp Cell Res2012;318:2168-77

[77] Dou H,Su G.Decreased plasma let-7c and miR-152 as noninvasive biomarker for non-small-cell lung cancer..Int J Clin Exp Med2015;8:9291-8 PMCID:PMC4538081

[78] Yu H,Sun C,Lin M.Decreased circulating miR-375: a potential biomarker for patients with non-small-cell lung cancer..Gene2014;534:60-5

[79] Heneghan HM,Lowery AJ,Newell J.Circulating microRNAs as novel minimally invasive biomarkers for breast cancer..Ann Surg2010;251:499-505

[80] Pérez-Ramírez C,Robles AI,Faus-Dáder MJ.Liquid biopsy in early stage lung cancer..Transl Lung Cancer Res2016;5:517-24 PMCID:PMC5099510

[81] Quandt D,Amann A,Borrebaeck C.Implementing liquid biopsies into clinical decision making for cancer immunotherapy..Oncotarget2018;8:48507-20 PMCID:PMC5564665

[82] Nikolaev S,Koessler T,Nouspikel T.Circulating tumoral DNA: Preanalytical validation and quality control in a diagnostic laboratory..Anal Biochem2018;542:34-9

[83] Barr J,Martínez-Arranz I,Alonso C.Obesity- dependent metabolic signatures associated with nonalcoholic fatty liver disease progression..J Proteome Res2012;11:2521-32 PMCID:PMC3321123

[84] Kim J.Isothermal DNA amplification in bioanalysis: strategies and applications..Bioanalysis2011;3:227-39

[85] D'Agata R.Surface plasmon resonance imaging for nucleic acid detection..Anal Bioanal Chem2013;405:573-84

[86] Das J,Montermini L,Sargent EH.An electrochemical clamp assay for direct, rapid analysis of circulating nucleic acids in serum..Nat Chem2015;7:569-75