Serum MicroRNA-21 as Marker for Necroinflammation in Hepatitis C Patients with and without Hepatocellular Carcinoma 英文参考文献.docVIP

Serum MicroRNA-21 as Marker for Necroinflammation in Hepatitis C Patients with and without Hepatocellular Carcinoma 英文参考文献.doc

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Serum MicroRNA-21 as Marker for Necroinflammation in Hepatitis C Patients with and without Hepatocellular Carcinoma 英文参考文献

SerumMicroRNA-21asMarkerforNecroinflammationin HepatitisCPatientswithandwithoutHepatocellular Carcinoma VerenaBihrer1.,OliverWaidmann1.,MireenFriedrich-Rust1,NicoleForestier1,SimoneSusser1,Jo¨rg Haupenthal1¤,MartinWelker1,YingShi1,JanPeveling-Oberhag1,AndreasPolta1,MichaelvonWagner1, HeinfriedH.Radeke2,ChristophSarrazin1,Jo¨rgTrojan1,StefanZeuzem1,BerndKronenberger1, AlbrechtPiiper1* 1DepartmentofMedicineI,UniversityofFrankfurt/M.,Frankfurt,Germany,2InstituteofPharmacology/ZAFES,UniversityofFrankfurt/M.,Frankfurt,Germany Abstract Background: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellularcarcinoma(HCC).ElevatedconcentrationsofmiR-21havealsobeenfoundinseraorplasmafrompatients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serummiR-21levelswithclinicalparametersinpatientswithdifferentstagesofchronichepatitisCvirusinfection(CHC)and CHC-associatedHCC. Methodology/Principal Findings: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectivelyenrolled.RNAwasextractedfromtheseraandmiR-21aswellasmiR-16levelswereanalyzedbyquantitative real-timePCR;miR-21levels(normalizedbymiR-16)werecorrelatedwithstandardliverparameters,histologicalgradingand staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls(P,0.001);therewasnodifferencebetweenserummiR-21inpatientswithCHCandCHC-associatedHCC.Serum miR-21levelscorrelatedwithhistologicalactivityindex(HAI)intheliver(r=20.494,P=0.00002),alanineaminotransferase (ALT) (r=20.309, P=0.007), aspartate aminotransferase (r=20.495, P=0.000007), bilirubin (r=20.362, P =0.002), internationalnormalizedratio(r=20.338,P=0.034)andc-glutamyltransferase(r=20.244,P=0.034).Multivariateanalysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dCT of 1.96, miR-21 discriminated bet

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