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 VCAN were genotyped by DNA sequencing. Prognostic values of VCAN 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 VCAN 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 (p<0.001, p=0.012, p=0.010, p=0.007, and p=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, p=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, p<0.001; and adjusted HR = 1.99, 95% CI = 1.12–3.55, p = 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 VCAN were associated with overall survival in patients with resected early-stage hepatitis B virus-associated HCC, and may be a potential prognostic biomarker.