Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Liu X

PROVIDER: S-EPMC5942399 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Liu Xiaoguang X Han Chuangye C Liao Xiwen X Yu Long L Zhu Guangzhi G Su Hao H Qin Wei W Lu Sicong S Ye Xinping X Peng Tao T

Cancer management and research 20180504

<h4>Background</h4>The upregulated expression of versican (VCAN) promotes the proliferation, invasion, and metastasis of various types of human cancer cells, including hepatocellular carcinoma (HCC) cells.<h4>Patients and methods</h4>In this study, genetic variants in the exon region of <i>VCAN</i> were genotyped by DNA sequencing. Prognostic values of <i>VCAN</i> exon single nucleotide polymorphisms (SNPs) were assessed by Kaplan-Meier with the log-rank test, and uni- and multivariate Cox propo ...[more]

PMID: 29765250

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Project description:Background & aimsSevere alcoholic hepatitis (AH) is a highly lethal condition and it is still a challenge to predict the outcome. We previously identified and validated a composite score of hepatic 123-gene prognostic signature and the model for end-stage liver disease (MELD) score: gene signature-MELD. However, the need for liver biopsy limits its clinical application. Therefore, we aimed to identify a plasma protein-based surrogate of the gene signature and independently validate its prognostic capability.MethodsAll patients were diagnosed with severe AH at Cliniques universitaires de Bruxelles Hôpital Erasme (Brussels, Belgium), and the plasma samples were collected at admission before any treatment. The primary outcome was death or liver transplantation within 90 days. Using our computational pipeline, named translation of tissue expression to secretome (TexSEC), a hepatic-transcriptome-based prognostic signature was converted to a plasma-based secretome signature, which was optimized in 50 patients by comparing their hepatic molecular dysregulation status and combining it with the MELD score. The composite score was validated independently in 57 patients.ResultsThe TexSEC and optimization process identified a 6-plasma-protein panel as a surrogate for the 123-gene signature. A composite score with the MELD score, the plasma-signature (ps)-MELD score, was created by using the coefficients of the gene signature-MELD equation. In the validation cohort, the high-risk ps-MELD (n = 23; 40%) was associated significantly with death or liver transplantation within 90 days (adjusted hazard ratio, 4.57; 95% CI, 2.15-9.30; P < .001). The ps-MELD score showed a stable, high prognostic association (time-dependent area under receiver operating characteristics curve, >0.80) and was well calibrated over time; it consistently outperformed existing clinical scores as indicated by various model performance indices.ConclusionsThe high-risk ps-MELD score was associated with short-term survival in patients with severe AH.

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

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

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