Analysis Of The Diagnostic Value Of Hsa＿circ＿0076251 Combined With Hsa＿circ＿0028502 In Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC)is a malignant tumor with high heterogeneity and poor prognosis,which ranks second in the mortality rate of malignant tumors in china.There were still many patients with HCC who were diagnosed at advanced stages by current diagnostic standards and therefor lost the best chance for treatment.Hence,it is very important to search for novel potential biomarkers to increase the rate of early detection.Circular RNAs(circRNAs)are a class of non-coding RNAs(nc RNAs),the 3′and 5′ends of which are covalently linked,showing different characteristics from linear RNAs.Circ RNAs harbor many features,such as stability,conservation,and tissue specificity.Emerging studies have shown that circRNAs were closely related to the development of HCC,and had significant advantages in the early diagnosis and prognosis evaluation of HCC.In this study,we screened out the differently regulated circRNAs,through microarray analysis.We then chosen two circRNAs,hsa＿circ＿0028502 and hsa＿circ＿0076251 for our further study.We aimed to determine hsa＿circ＿0028502 and hsa＿circ＿0076251 expression profile in HCC by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),investigate their clinical significances and evaluate diagnostic power.Our data demonstrate that the hsa＿circ＿0028502 and hsa＿circ＿0076251 levels were significantly decreased in HCC tissues compared to adjacent para-cancerous tissues(P<0.001).Further study revealed that hsa＿circ＿0028502 expression levels were related to tumor-node-metastasis(TNM)stage(P=0.015)and hsa＿circ＿0076251 expression levels were related to diabetes mellitus(P=0.023),BCLC stage(P=0.038)and serum α-fetoprotein(AFP)levels(P=0.044).Furthermore,the degree of hsa＿circ＿0028502 and hsa＿circ＿0076251 expression levels were both decreased successively from chronic hepatitis(CH)to liver cirrhosis(LC)to HCC.The receiver operating characteristic curve(ROC)demonstrated that hsa＿circ＿0028502 and hsa＿circ＿0076251could be fairly accurate markers to distinguish HCC tissues from LC tissues and CH tissues as well as LC tissues from CH tissues.Survival curve analysis showed that HCC patients with high expression of has＿circ＿0076251 had longer survival time than those with low expression of has＿circ＿0076251(HR=0.46;95% CI=0.22-0.98;P< 0.05).Multivariate Cox regression analysis suggested that has＿circ＿0076251 was an independent prognostic factor for HCC patients.In summary,our study demonstrated that hsa＿circ＿0028502 and hsa＿circ＿0076251 are potentially valuable biomarkers for HCC diagnosis,meanwhile,hsa＿circ＿0076251 could serve as a prognostic indicator for HCC.