Circular RNA SMARCA5 Promotes a Poor Prognosis and Radiotherapy Resistance for Patients with Hepatocellular Carcinoma

Objective: The involvement of Circular RNA SMARCA5 (cSMARCA5) in several types of cancer has been reported; however, its role in hepatocellular carcinoma (HCC) is unclear. The presented research aimed to explore the expression level of cSMARCA5 in HCC tissues and evaluate the association between cSMARCA5, prognosis, and radiotherapy resistance for patients with HCC.

Methods: This study was designed as a case controlled study and enrolled 106 HCC patients. HCC and paired non-tumor samples were collected from HCC patients. Gene expression was analyzed by RT-qPCR. The association between the expression level of cSMARCA5 and prognosis value and radiotherapy resistance for patients with HCC was analyzed by Kaplan-Meier survival curve and Multivariate Cox analysis.

Results: Compared to paracancerous tissue, cSMARCA5 demonstrated higher expression in the tumor tissues (p<0.0001).Higher expression of cSMARCA5 is a risk factor in 3-year overall survival (OS) for HCC patients (HR=1.798, 95%CI: 1.165~3.231, p=0.0321). Multivariate analysis showed that higher expression of cSMARCA5 was related to PVTT (HR=2.136, 95%CI: 1.130~5.218), AFP (>400ng/ml) (HR=2.335, 95%CI: 1.247~5.661), tumor size (>5cm) (HR=3.017, 95%CI: 1.477~5.659), poor histopathologic grading (HR=3.344, 95%CI: 2.175~6.143), and multiple tumor number (HR=2.875, 95%CI: 1.453~3.884). We also found that radiotherapy resistance was related to AFP (>400ng/ml) (OR=2.125, 95%CI: 1.015~3.348), tumor size (>5cm) (OR=2.857, 95%CI: 1.665~4.978), poor histopathologic grading (OR=2.463, 95%CI: 1.389~4.446), multiple tumor number (OR=2.332, 95%CI: 1.538~3.887), and high expression of cSMARCA5 (OR=3.574, 95%CI: 1.663~5.932).

Conclusion: CircRNA-SMARCA5 is significantly increased in HCC tissues and promotes radiotherapy resistance. More importantly, higher expression level of cSMARCA5 is related to a poorer 3-year OS for patients with HCC.