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

Peng Wang; Liang-Liang Xu; Xiao-Bo Zheng; Yi-Tao Hu; Jin-Fu Zhang; Sheng-Sheng Ren; Xiang-Yong Hao; Lian Li; Ming Zhang; Ming-Qing Xu

doi:10.21037/atm.2020.02.134

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

Ann Transl Med. 2020 Mar;8(6):338. doi: 10.21037/atm.2020.02.134.

Authors

Peng Wang¹, Liang-Liang Xu¹, Xiao-Bo Zheng¹, Yi-Tao Hu¹, Jin-Fu Zhang¹, Sheng-Sheng Ren¹, Xiang-Yong Hao^{1

2}, Lian Li¹, Ming Zhang^{1

3}, Ming-Qing Xu¹

Affiliations

¹ Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
² Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, China.
³ Department of General Surgery, Mianzhu Hospital of West China Hospital, Sichuan University, Mianzhu 618200, China.

Abstract

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.

Keywords: Circular RNAs (circRNAs); hepatocellular carcinoma (HCC); microvascular invasion (MVI); prothrombin induced by vitamin K absence-II (PIVKA-II).