MicroRNA signature in patients with hepatocellular carcinoma associated with type 2 diabetes

查看全文 作　　者：Moustafa Nouh [1,2,3,4]Elemeery;Marwa Anwar [5]Mohamed;Marwa Ahmed [6]Madkour;Mohammed Mohammed [6]Shamseya;Noha Mahmoud [7]Issa;Ahmed Noah [8]Badr;Doaa Ahmed [9,10]Ghareeb;Cheol-Ho [3,4]Pan

机构地区：[1]Département de Neurosciences,CRCHUM,Universitéde Montréal,Montréal,Quebec H2X 3E4,Canada;[2]Medical Biotechnology Laboratory,Genetic Engineering and Biotechnology Research Division,National Research Centre,Cairo 12622,Egypt;[3]Natural Product Informatics Research Center,KIST Gangneung Institute of Natural Products,Gangneung 25451,South Korea;[4]Division of Bio-Medical Science and Technology,KIST School,Korea University of Science and Technology,Seoul 02792,South Korea;[5]Department of Chemical Pathology,Medical Research Institute,Alexandria University,Alexandria 21511,Egypt;[6]Experimental and Clinical Internal Medicine Department,Medical Research Institute,Alexandria University,Alexandria 21511,Egypt;[7]Human Genetics Department,Medical Research Institute,Alexandria University,Alexandria 21511,Egypt;[8]Food Toxicology and Contaminates Department,National Research Centre,Dokki,Cairo 12622,Egypt;[9]Bioscreening and preclinical trial lab,Biochemistry Department,Faculty of Science,Alexandria University,Alexandria 12522,Egypt;[10]Pharmaceutical and fermentation industries development center,the city of scientific research and technological applications,Alexandria 26411,Egypt

出　　处：《World Journal of Gastroenterology》索引2019年第25卷第42期,共20页

基　　金：support from the National Research Centre (Cairo, Egypt), Medical Research Institute (Alexandria, Egypt) and Korea Institute of Science and Technology (Republic of Korea, 2Z05620) 摘　　要：BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus(T2DM)and reported to be a risk factor for developing hepatocellular carcinoma(HCC).A reliable screening biomarker of liver cirrhosis(LC)and HCC among T2DM patients is important to reduce the morbidity and mortality of this disease.MicroRNA(miRNA)is considered a key player in HCC and T2DM,and it might be a hidden culprit in diabetes-associated HCC,making it a promising reliable prognostic tool.AIM To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic patients.METHODS Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing;then,RT-qPCR was used to validate significantly altered miRNAs between the two groups.Candidate miRNAs were tested in serum samples of 200 T2DM patients,270 LC patients,200 HCC patients,and 225 healthy control subjects.Additionally,receiver operating characteristic(ROC)analysis,with area under the curve(AUC),was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients(LC+T2DM).RESULTS Expression of the sequenced miRNAs in serum was different in HCC vs LCpositive T2DM patients.Two miRNAs(miR-34a,miR-221)were significantly upregulated and five miRNAs(miR-16,miR-23-3p,miR-122-5p,miR-198,miR-199a-3p)were significantly down-regulated in HCC compared to LC patients.Analysis of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients,as it could identify HCC with high diagnostic accuracy in diabetic LC patients(AUC=0.993)and in diabetic nonmalignant patients(AUC=0.961).CONCLUSION This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic patients.The study recommends further research to shed light on a possible role of c-Met in T2DM-associated HCC via the miRNA regulatory pathway. 关键词：MICRORNA HEPATOCELLULAR carcinoma Type 2 DIABETES NONALCOHOLIC FATTY liver disease

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MicroRNA signature in patients with hepatocellular carcinoma associated with type 2 diabetes

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