Expression of circular RNA FLI1 in patients with hepatocellular carcinoma and its association with prognosis

Objective To investigate the expression and significance of circular RNA FLI1 ( circ FLI1) in patients with hepatocellular carcinoma ( HCC) . Methods A total of 45 HCC patients who underwent surgical resection in The Affiliated Hospital of Southwest Medical University from January 2013 to January 2018 were enrolled as HCC group, and the samples of cancerous tissue, adjacent tissue, and serum were collected. A total of 45 healthy individuals who underwent physical examination were enrolled as control group, and their serum samples were collected. Human hepatoma cell lines HepG2, SMMC7721, and HB611 were obtained from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences. qRT-PCR was used to measure the expression of circ FLI1 in hepatoma cells and 45 samples of cancerous tissue and serum. The t-test was used for comparison of continuous data between groups. The Kaplan-Meier method was used to analyze the association between circ FLI1 expression and survival time; the receiver operating characteristic ( ROC) curve was used to evaluate the potential of serum circ FLI1 E2-4 and circ FLI1 E2-5 as the biomarkers for the diagnosis of HCC; univariate and multivariate Cox proportional hazards model analyses were used to investigate the influencing factors for the prognosis of HCC. Results There was high expression of circ FLI1 E2-5 and circ FLI1 E2-4 in the three hepatoma cell lines. Compared with the control group, the HCC group had sig-nificantly higher serum levels of circ FLI1 E2-4 ( 7. 09 ± 0. 26 vs 1. 14 ± 0. 20, t = 19. 970, P < 0. 001) and circ FLI1 E2-5 ( 7. 50 ±0. 25 vs 1. 29 ± 0. 30, t = 16. 640, P < 0. 001) . For the HCC patients, the expression of circ FLI1 E2-4 and circ FLI1 E2-5 in cancerous tissue was significantly higher than that in adjacent tissue ( circ FLI1 E2-4: 7. 62 ± 1. 33 vs 1. 55 ± 0. 32, t = 15. 560, P < 0. 001; circ FLI1 E2-5: 7. 92 ± 0. 35 vs 1. 42 ± 0. 39, t = 21. 170, P < 0. 001) . The patients with high expression of circ FLI1 E2-5 had significantly shorter median progression-free survival time and overall survival time than those with low expression ( median progression-free survival time: 11. 17 ± 0. 49 months vs 23. 35 ± 1. 27 months, χ2= 28. 480, P < 0. 001; overall survival time: 19. 75 ± 0. 76 months vs 37. 44 ± 1. 57 months, χ2= 21. 750, P < 0. 001) . The patients with high expression of circ FLI1 E2-4 had significantly shorter median progression-free survival time and overall survival time than those with low expression ( median progression-free survival time: 10. 29 ± 0. 42 months vs 24.65 ± 1. 58 months, χ2= 19. 620, P < 0. 001; overall survival time: 21. 32 ± 0. 55 months vs 35. 69 ± 1. 74 months, χ2= 19. 730, P < 0.001) . As a serum marker for the diagnosis of HCC, serum circ FLI1 E2-4 had an area under the ROC curve of 0. 910 ( 95% confidence interval [CI]: 0. 621-0. 970, P < 0. 001) , with a sensitivity of 84. 3% and a specificity of 90. 5%. As a serum marker for the diagnosis of HCC, serum circ FLI1 E2-5 had an area under the ROC curve of 0. 760 ( 95% CI: 0. 650-0. 860, P < 0. 001) , with a sensitivity of80. 5% and a specificity of 87. 3%. The multivariate Cox proportional hazards model analysis showed that serum circ FLI1 E2-4 ( hazard ratio [HR]= 3. 060, 95% CI: 1. 630-5. 870, P < 0. 05) and circ FLI1 E2-5 ( HR = 2. 560, 95% CI: 1. 250-6. 460, P < 0. 05) were independent influencing factors for the prognosis of HCC patients. Conclusion Circ FLI1 is highly expressed in the tissue and serum of HCC patients, which is associated with the prognosis of patients. It may be a potential biomarker for prognosis and a therapeutic target for HCC.