MicroRNAs Of Peripheral Blood For The Diagnosis Of Hepatocellular Carcinoma:a Meta-analysis

Aims:The present study aims to evaluate the diagnostic effectiveness of miRNAs of peripheral blood for HCC through evidence-based medicine system and provide scientific basis for further research and clinical application.Methods:Based on the following six databases,we conducted a comprehensive literature search to identify the studies that evaluated the diagnostic accuracy of miRNAs of peripheral blood for HCC:PubMed,Embase,Cochrane Library,Chinese National Knowledge Infrastructure,WanFang Database,and VIP.We also performed a manual search of the reference lists of review articles to obtain potential relevant studies.The basic information and diagnostic data were extracted from eligible studies,which were included according to the selection criteria.The pooled analysis was performed by statistical software including STATA 14,Meta-disc and Revman 5.3.Results:Apply miRNAs only,the pooled sensitivity and specificity for discriminating HCC from non-HCC controls were 0.80(95%CI:0.78-0.82)and 0.74(95%CI:0.71-0.76),respectively,the positive likelihood ratio,negative likelihood ratio,diagnostic odds ratio and the area under curve were 3.05(95%CI:2.81-3.30),0.27(95%CI:0.24-0.30),11.37(95%CI:9.79-13.20)and 0.84(95%CI:0.80-0.87),respectively.MiRNAs panels improved the diagnostic power with an increase in sensitivity of 0.84(95%CI:0.80-0.87),specificity of 0.87(95%CI:0.83-0.90),positive likelihood ratio of 6.62(95%CI:4.97-8.81),diagnostic odds ratio of 35.53(95%CI:22.88-55.18),area under curve of 0.92(95%CI:0.89-0.94)as well as a decrease in negative likelihood ratio of 0.19(95%CI:0.15-0.23),the combination of miRNAs and AFP could further improve the diagnostic efficiency.In addition,miRNAs exhibited a satisfactory diagnostic effectiveness for HCC patients at early stage and HCC patients with low AFP or negative AFP levels.The results showed that miRNAs yield a sensitivity of 0.82(95%CI:0.78-0.85),specificity of 0.69(95%CI:0.61-0.77)and the area under curve were 0.84(95%CI:0.81-0.87)in discriminating early-staged HCC from non-HCC controls.For HCC patients with low AFP level,the overall sensitivity and specificity of circulating miRNAs were 0.83(95%CI:0.78-0.88)and 0.77(95%CI:0.70-0.83),respectively.The corresponding the area under curve value was 0.88(95%CI:0.84-0.90).For HCC patients with negative AFP level,the overall sensitivity and specificity of miRNAs were 0.82(95%CI:0.77-0.85)and 0.77(95%CI:0.67-0.84),respectively.The corresponding the area under curve value was 0.85(95%CI:0.81-0.88).Conclusions:The peripheral blood miRNAs detection is superior than AFP which provide satisfactory diagnostic accuracy for HCC.The combination of miRNAs and AFP provides a more satisfactory diagnostic performance than either AFP or miRNA alone.In addition,miRNA detection is benefit for the diagnosis of HCC patients with AFP negative.Therefore,miRNA detection can provide a powerful tool with AFP for the earlier diagnosis or screening of HCC.Combination of miRNA and AFP could significantly increase the potential of earlier diagnostic rate of HCC.