Feasibility of Fecal MicroRNAs as Novel Biomarkers for Pancreatic Cancer 英文参考文献.docVIP

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Feasibility of Fecal MicroRNAs as Novel Biomarkers for Pancreatic Cancer 英文参考文献.doc

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Feasibility of Fecal MicroRNAs as Novel Biomarkers for Pancreatic Cancer 英文参考文献

FeasibilityofFecalMicroRNAsasNovelBiomarkersfor PancreaticCancer AlexanderLink1*,VerenaBecker1,AjayGoel2,ThomasWex1,PeterMalfertheiner1 1Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany, 2Gastrointestinal Cancer Research Laboratory,DivisionofGastroenterology,BaylorResearchInstitute,BaylorUniversityMedicalCenter,Dallas,Texas,UnitedStatesofAmerica Abstract Introduction: Pancreatic cancer (PCA) is an aggressive tumor that associates with high mortality rates. Majority of PCA patients are diagnosed usually at late tumor stages when the therapeutic options are limited. MicroRNAs (miRNA) are involvedintumordevelopmentandarecommonlydysregulatedinPCA.Asaproof-of-principlestudy,weaimedtoevaluate thepotentialoffecalmiRNAsasbiomarkersforpancreaticcancer. MaterialsandMethods:TotalRNAwasextractedfromfecesusingQiagen’smiRNAMiniKit.FormiRNAexpressionanalyses we selected a subset of 7 miRNAs that are frequently dysregulated in PCA (miR-21, -143, -155, -196a, -210, -216a, -375). Subsequently, expression levels of these miRNAs were determined in fecal samples from controls (n=15), chronic pancreatitis(n=15)andPCApatients(n=15)usingquantitativeTaqMan-PCRassays. Results:AllselectedmiRNAsweredetectableinfecalsampleswithhighreproducibility.FourofsevenmiRNAs(miR-216a,- 196a,-143und-155)weredetectedatlowerconcentrationsinfecesofPCApatientswhencomparedtocontrols(p,0.05). AnalysisoffecalmiRNAexpressionincontrolsandpatientswithchronicpancreatitisandPCArevealedthattheexpression of miR-216a, -196a, -143 und -155 were highest in controls and lowest in PCA. The expression of the remaining three miRNAs(miR-21,-210and-375)remainedunchangedamongcontrolsandthepatientswitheitherchronicpancreatitisor PCA. Conclusion: Our data provide novel evidence for the differential expression of miRNAs in feces of patients with PCA. If successfullyvalidatedinlarge-scaleprospectivestudies,thefecalmiRNAbiomarkersmayoffernoveltoolsforPCAscreening re