Using circular RNA SMARCA5 as a potential novel biomarker for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common malignant tumor worldwide. Circular RNAs (circRNAs), a new class of endogenous non-coding RNAs, are widespread and abundant in mammalian cells. Cumulative evidence showed that circRNAs play significant roles in the process of cancer. However, the expression and function of circRNAs in HCC remain to be investigated.

Methods: The expression of circular RNA SMARCA5 (circSMARCA5) in tissues and plasma samples was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The role of circSMARCA5 in HCC progression was assessed by in vitro experiments. A receiver operating characteristic (ROC) curve was established to evaluate the value of circSMARCA5 as a biomarker in HCC.

Results: The expression of circSMARCA5 was significantly downregulated in HCC tissues compared with para-carcinoma tissues. CircSMARCA5 levels were correlated with tumor differentiation (p = 0.023), Tumor-node-metastasis (TNM) stage (p = 0.001), cancer invasion (p = 0.004), as well as cancer diameter (p = 0.018). In vitro cell experiments revealed that overexpression of circSMARCA5 resulted in inhibited proliferation, increased apoptosis and suppressed invasion. Moreover, we found that circSMARCA5 expression was down-regulated in plasma samples of patients with HCC. The ROC curve analyses revealed that plasma circSMARCA5 showed a high accuracy (AUC = 0.938, 0.853, 0.711) for diagnosing HCC from healthy controls, hepatitis and cirrhosis. The area under the ROC curve of plasma circSMARCA5 in combination with AFP in diagnosing HCC from hepatitis and cirrhosis was 0.903 and 0.858. Especially, plasma circSMARCA5 presented a high accuracy (AUC = 0.847, 0.706) for detecting HCC with serum AFP below 200 ng/ml from those hepatitis and cirrhosis with AFP below 200 ng/ml.

Conclusion: Our study revealed that circSMARCA5 may promote apoptosis, inhibit proliferation, invasion and metastasis of HCC cells. CircSMARCA5 may serve as a potential prediction and monitor biomarker for HCC, especially in HCC patients with AFP blow the cutoff value.