RESUMO
Copy number aberrations (CNAs) in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma (HCC).This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients,and further screen for differentially expressed genes in outcome-related CNAs.Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels,respectively.The correlations between CNAs in 8q and outcomes were analyzed in 66 patients,with a median follow-up time of 45.0 months (range,2.6-108.6 months).One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs.Copy number gain in 8q was observed in 22 (33.3 ％) of the 66 HCC cases.The most recurrent gains (with frequencies ＞20％) were 8q13.3-21.3,8q21.3-23.3,8q23.3-24.13,8q24.13-24.3,and 8q24.3.Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival (P=0.010).Multivariate Cox analysis identified 8q24.13-24.3 gain as an independent prognostic factor for poor overall survival (HR=2.47;95％CI=1.16-5.26;P=0.019).A panel of 17 genes within the 8q24.13-24.3 region,including ATAD2,SQLE,PVT1,ASAP1,and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without.These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients,and the potential oncogenes ATAD2,SQLE,PVT1,ASAP1,and NDRG1 within the regional gain,may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.
RESUMO
Copy number aberrations (CNAs) in chromosome arm 8q have been associated with unfavorable clinical outcomes of several cancers and progressive tumor characteristics of hepatocellular carcinoma (HCC).This study was to identify correlation of CNAs in 8q with clinical outcomes of HCC patients,and further screen for differentially expressed genes in outcome-related CNAs.Array comparative genomic hybridization and expression arrays were performed to detect CNAs and expression levels,respectively.The correlations between CNAs in 8q and outcomes were analyzed in 66 patients,with a median follow-up time of 45.0 months (range,2.6-108.6 months).One hundred and nine cases were further evaluated to identify differentially expressed genes in the potential outcome-related CNAs.Copy number gain in 8q was observed in 22 (33.3 ％) of the 66 HCC cases.The most recurrent gains (with frequencies ＞20％) were 8q13.3-21.3,8q21.3-23.3,8q23.3-24.13,8q24.13-24.3,and 8q24.3.Survival analysis showed that 8q24.13-24.3 gain was significantly associated with reduced overall survival (P=0.010).Multivariate Cox analysis identified 8q24.13-24.3 gain as an independent prognostic factor for poor overall survival (HR=2.47;95％CI=1.16-5.26;P=0.019).A panel of 17 genes within the 8q24.13-24.3 region,including ATAD2,SQLE,PVT1,ASAP1,and NDRG1 were significantly upregulated in HCCs with 8q24.13-24.3 gain compared to those without.These results suggest that copy number gain at 8q24.13-24.3 is an unfavorable prognostic marker for HCC patients,and the potential oncogenes ATAD2,SQLE,PVT1,ASAP1,and NDRG1 within the regional gain,may contribute coordinately to the 8q24.13-24.3 gain-related poor prognosis.
RESUMO
Objective@#To investigate the molecular markers of copy number aberrations (CNAs) of genes related to extrohepatic metastasis-free survival after the operation for hepatocellular carcinoma (HCC).@*Methods@#The CNA status of 20 candidate genes in 66 HCC samples was detected by microarray comparative genomic hybridization. The associations between gene CNAs and extrohepatic metastasis-free survival were evaluated using the Cox regression model, Log-rank test, and Kaplan-Meier survival analysis.@*Results@#Multivariate Cox analysis revealed that the independent risk factors for metastasis-free survival were MDM4 gain (hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.18-6.37, P < 0.05), APC loss (HR = 8.43, 95% CI = 2.48-28.66, P < 0.01), and BCL2L1 gain (HR = 3.45, 95% CI = 1.13-10.52, P < 0.05) and the independent protective factor was FBXW7 loss (HR = 0.32, 95% CI = 0.12-0.89, P < 0.05). By stepwise Cox regression analysis, three CNAs related to metastasis-free survival were screened out: MDM4 gain (HR = 2.71, 95% CI = 1.11-6.64, P < 0.05), APC loss (HR = 7.19, 95% CI = 1.88-27.60, P < 0.005), and FBXW7 loss (HR = 0.16, 95% CI = 0.05-0.46, P < 0.01). There were significant differences in metastasis-free survival rate between the HCC patients with FBXW7 loss and without MDM4 gain or APC loss, those with MDM4 gain and/or APC loss and without FBXW7 loss, and those with other CNA combinations (log-rank test, P < 0.01).@*Conclusion@#MDM4 gain, APC loss, and FBXW7 loss are the independent prognostic factors for extrohepatic metastasis-free survival after the operation for HCC and can be used to predict the risk of extrohepatic metastasis after the operation for HCC.
RESUMO
RAN-aCGH is an R GUI tool for the analysis and visualization of array comparative genomic hybridization (array-CGH) experiments. The tool consists of data-loading, preprocessing for missing data, several methods for statistical identification of DNA copy number aberration, and visualization of the copy number change. RAN-aCGH requires a single input format, provides various visualizations, and allows the addition of a new statistical method, all in a user-friendly graphic user interface (GUI).