Loss at 16q22.1 identified as a risk factor for intrahepatic recurrence in hepatocellular carcinoma and screening of differentially expressed genes

摘要

Copy number alteration (CNA) of chromosome 16, a frequent genetic event in tumors including hepatocellular carcinoma (HCC), has been associated with HCC etiology of hepatitis B virus (HBV) and with clinical outcomes in multiple types of cancer. This study identified CNAs in chromosome 16 in relation to intrahepatic recurrence of HCC in a population with high HBV prevalence, and further screened for differentially expressed genes in recurrence-related CNAs. Array comparative genomic hybridization and expression arrays were used to detect CNAs and gene expression differences, respectively. The associations between CNAs and intrahepatic recurrence were analyzed on 66 patients, follow-up period of 3-73 months. One hundred and nine cases were further evaluated regarding the differentially expressed genes. Losses at 16q and 16p were detected in 62.1% and 51.5% of the 66 cases, respectively. The most recurrent CNAs (with frequency >20%) were losses at 16p13.3-13.2, 16p13.11, 16q11.2-22.1, 16q22.1, 16q22.2-24.2 and 16q24.2. Of the CNAs, 16q22.1 loss was significantly associated with unfavorable intrahepatic recurrence-free survival (P = 0.025). Multivariate Cox analysis identified 16q22.1 loss as an independent risk factor for intrahepatic recurrence (HR = 2.32, 95% CI = 1.26-4.27). A panel of 21 genes, including TRADD, PSMB10, THAP11, CTCF and ESRP2, were significantly downregulated in HCCs with 16q22.1 loss compared to those without the loss. These results suggest that loss at 16q22.1 was associated with increased risk for intrahepatic recurrence of HCC, at least in the HBV-prevalence population. Multiple downregulated genes correlated with the loss were screened.