Background and Aims: Long non-coding RNA HULC (lncRNA HULC) is specifically highly expressed in hepatocellular carcinoma (HCC), and is an important tumor marker of HCC. This study was conducted to investigate the relations of serum lncRNA HULC level with the clinical features and prognosis of patients with hepatitis B virus-related HCC (HBV-related HCC). 
Methods: The samples of serum and surgical specimens of 30 patients with HBV-related HCC undergoing surgical treatment from June 2012 to September 2017 were collected. The relative levels of lncRNA HULC in the serum of the patients were determined by qRT-PCR, and the expressions of tumor invasion/metastasis-associated markers VEGF, MMP-2 and E-cadherin in the cancer tissues of the patients were detected by immunohistochemical staining. The relations of serum lncRNA HULC level with the clinicopathologic factors and expressions of tumor invasion/metastasis-associated markers as well as the prognosis of the patients were analyzed.
Results: The relative level of serum lncRNA HULC of the patients ranged from 2.6 to 9.5. Using the median value of 5.0 as the threshold, the patients were divided into high lncRNA HULC group (12 cases) and low lncRNA HULC group (18 cases). Results of statistical analysis showed that the proportion of cases with high pathological differentiation in low lncRNA HULC group was significantly higher than that in high lncRNA HULC group; the proportion of stage III-IV cases in high lncRNA HULC group was significantly higher than that in low lncRNA HULC group; the proportion of cases with intrahepatic and distant metastasis in low lncRNA HULC group was significantly lower than that in high lncRNA HULC group; the proportion of cases with recurrence in high lncRNA HULC group was significantly higher than that in low lncRNA HULC group, and all the differences had statistical significance (all P<0.05). Results of immunohistochemical staining showed that the positive expressions of tumor invasion/metastasis-promoting proteins VEGF and MMP-2 were increased while the tumor invasion/metastasis-suppressing protein E-cadherin was decreased in HCC tissues from patients in high lncRNA HULC group compared with those in low lncRNA HULC group. Results of Kaplan-Meier analysis showed that the survival rate of patients in high lncRNA HULC group was lower than that of patients in low lncRNA HULC group, and the recurrence rate of patients in high lncRNA HULC group was higher than that of patients in low lncRNA HULC group (both P<0.05). Results of Cox proportional hazard regression analysis showed that preoperative serum lncRNA HULC level was an independent influencing factor for the prognosis of patients with HBV-related HCC (OR=1.769, P=0.045).
Conclusion: The serum lncRNA HULC level is closely related to the malignant clinical features of patients with HBV-related HCC, and those with high serum lncRNA HULC level may face a poor prognosis.