Genetic variants in the exon region of versican predict survival of patients with resected early-stage hepatitis B virus-associated hepatocellular carcinoma.

Background: The upregulated expression of versican (VCAN) promotes the proliferation, invasion, and metastasis of various types of human cancer cells, including hepatocellular carcinoma (HCC) cells.

Patients And Methods: In this study, genetic variants in the exon region of were genotyped by DNA sequencing. Prognostic values of exon single nucleotide polymorphisms (SNPs) were assessed by Kaplan-Meier with the log-rank test, and uni- and multivariate Cox proportional hazard regression model.

Results: A total of 111 patients with resected hepatitis B virus-associated early-stage HCC were collected for genotyping exon SNPs using Sanger DNA sequencing. Haplotype analysis was performed using Haploview 4.2. Survival data were analyzed using Kaplan-Meier curves and Cox proportional hazards regression analyses. The rs2652098, rs309559, rs188703, rs160278, and rs160277 SNPs were significantly associated with overall patient survival (<0.001, =0.012, =0.010, =0.007, and =0.007, respectively). Patients carrying the TAGTG haplotype had a poorer prognosis than those with the most common CGAAT haplotype, after adjusting for tumor size, tumor capsule, and regional invasion (adjusted hazard ratio [HR] =2.06, 95% CI: 1.27-3.34, =0.003). Meanwhile, patients with the TAGTG haplotype and a larger tumor size or an incomplete tumor capsule had an increased risk of death, compared with the others (adjusted HR =3.00, 95% CI: 1.67-5.36, <0.001; and adjusted HR = 1.99, 95% CI = 1.12-3.55, = 0.02, respectively). The online database mining analysis showed that upregulated VCAN expression in HCC tissues was associated with a poor overall survival of 148 HCC patients.

Conclusion: Genetic variants in the exon region of were associated with overall survival in patients with resected early-stage hepatitis B virus-associated HCC, and may be a potential prognostic biomarker.