Association of chromosome 8p copy number alteration with postoperative survival of patients with hepatocellular carcinoma and screening of potential target genes / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the association of chromosome 8p copy number alteration (CNA) with postoperative survival of patients with hepatocellular carcinoma (HCC),and to screen for possible target genes in the survival-related CNA (s) in 8p.Methods 187 HCC patients were enrolled into the study,which included 66 patients whose follow-up data were available and the follow-up was 2.6 ～ 73.3 months.High-resolution Agilent 244K comparative genomic hybridization (CGH) and Affymetrix U133 Plus2.0 expression arrays were used to screen for CNAs and gene expression differences in 8p.The associations between CNAs in 8p and survival were analyzed using the log-rank test,Kaplan-Meier survival analysis and Cox proportional hazards models.The gene expression levels between the groups were compared by the Mann-Whitney U test.Results Copy number loss on 8p12 (31/66,47％) was significantly associated with reduced survival rate,and HCC patients with 8p12 loss had a 4.1-fold (95％ CI =1.8 ～ 9.4,P ＜ 0.05) increased hazard ratio (HR) for death from HCC,as compared to those without the loss.The mRNA expression levels of the 3 genes in 8p12,including TMEM66,DCTN6,and MAK16,were significantly decreased in HCCs with gene loss than in HCCs without the loss (all P ＜ 0.05),and in non-tumorous liver tissues (all P ＜ 0.05).Conclusion Loss of 8p12 is an independent prognostic marker of unfavorable survival for patients with HCC,and underexpression of genes TMEM66,DCTN6,and MAK16,owing to 8p12 loss,contributed to unfavorable prognosis.