Validation of a serum microRNA panel as biomarkers for early diagnosis of hepatocellular carcinoma post-hepatitis C infection in Egyptian patients

AIM To investigate the prospective importance of serum micro(mi)RNAs(mi R-125 b, mi R-138 b, mi R-1269, mi R-214-5p, mi R-494, mi R375 and mi R-145) as early biomarkers for the diagnosis of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS Two-hundred and fifty HCV4 a patients, 224 HCV4 aHCC patients, and 84 healthy controls were enrolled in the study. Expression levels of mi R214-5p, mi R-125 b, mi R-1269 and mi R-375 were quantified using quantitative real-time PCR.RESULTS Expression of the selected mi RNAs in serum wassignificantly lower in HCC patients than in the healthy controls, except for mi R-1269 and mi R-494. There was a significant difference between HCC and HCV patients, in particular for HCC and late stage fibrosis, rather than HCV patients and early fibrosis. It is obvious that mi R-1269 was significantly upregulated in HCC cases compared to hepatic fibrosis cases. Each mi RNA can show HCC progression. Multivariate logistic regression analysis indicated that the tested panel of mi RNAs(mi R214-5p, mi R-125 b, mi R-1269 and mi R-375) represent accurate and specific indictors of HCC development.CONCLUSION This study presents a panel of mi RNAs with strong power as putative diagnostic and prognostic biomarkers for HCV-induced HCC. Moreover, mi R-214-5p and mi R-1269 could be considered as early biomarkers for tracking the progress of liver fibrosis to HCC.

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

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.