Correlation between the expressions of circular RNAs in peripheral venous blood and clinicopathological features in hepatocellular carcinoma

BACKGROUND: Recent studies have reported that circular RNAs (circRNAs) are involved in the development of hepatocellular carcinoma (HCC). This study evaluated the expression of preoperative peripheral venous blood circRNAs in HCC patients and their predictive ability for microvascular invasion (MVI). METHODS: Seven circRNAs (circMTO1, circ-10720, circZKSCAN1, cSMARCA5, circHIPK3, circSETD3 and ciRS-7) were screened from the literature as circRNAs with reported biological functions in HCC. The expression levels of seven circRNAs in preoperative blood samples and HCC tissues were detected by quantitative reverse transcription polymerase chain reaction. The correlations between the circRNA expressions in blood and the clinicopathological factors of HCC patients were analyzed. The risk factors of MVI were analyzed by univariate and multivariate logistic regression. The functional role of circSETD3 in cell migration and invasion was evaluated by wound healing and Transwell assays in vitro. RESULTS: The expressions of all seven circRNAs were measured in peripheral venous blood samples. The venous expression levels of circHIPK3 and circMTO1 were significantly associated with gender, while circ-10720 and circMTO1 levels were significantly correlated with gross vascular invasion. Furthermore, circMTO1 and cSMARCA5 levels were significantly associated with alpha-fetoprotein level and ciRS-7 was significantly associated with satellite nodules. Importantly, low venous circSETD3 expression was significantly associated with prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) level, MVI, gross vascular invasion, and liver capsule. Furthermore, venous circSETD3 expression had predictive ability for MVI. Knockdown of circSETD3 promoted cell invasion and metastasis in vitro. CONCLUSIONS: CircRNAs were stably present in peripheral venous blood and associated with multiple clinicopathological characteristics of HCC patients. Venous circSETD3 was an independent risk factor of MVI and shows ability to predict MVI in HCC patients before surgery.