As shown in Fig. 4, TRIM35 was observed to not only arrest the cell cycle at G2/M phase but also to promote cell apoptosis of HCC cells overexpressing TRIM35, indicating that one mechanism by which TRIM35 inhibits HCC cell Tyrosine Kinase Inhibitor Library price proliferation is through impeding the cell cycle progression or inducing apoptotic cell death. To further determine the clinicopathologic significance of TRIM35 in HCC, we performed immunohistochemical (IHC) analysis of TRIM35 in a tissue array that included an independent set of 207 paired

HCC and adjacent noncancerous tissues as well as 10 normal liver and 16 cirrhosis tissues. As shown in Fig. 5A,B, not only was the protein level of TRIM35 sharply decreased in HCC tissues compared with matched noncancerous Alectinib tissues, normal liver samples or cirrhosis tissues, but the proportion of HCC specimens with TRIM35 underexpression was also predominant, which is consistent with our genomic and transcriptional results (Fig. 5C,D). Importantly, the expression level of TRIM35 was negatively correlated with tumor grade, tumor size, and serum alpha-fetoprotein (AFP) level (Table 2). However, the down-regulation of TRIM35 expression has no significant correlation with overall survival of HCC patients (data not shown). Taken together, these results suggested that loss of TRIM35 expression is

a critical event in the development and progression of HCC. Copy number alterations represent a substantial category of genetic variations. During carcinogenesis, cancer genomes often acquire somatic copy number changes, which can alter the dosage of oncogenes and tumor suppressors.1 Although several previous selleck chemicals llc studies have applied copy number analyses for HCC,12-14 in the present study we mainly focused on identifying CNAs and their associated oncogenes and tumor suppressors in HCC genomes using high-resolution SNP 6.0 arrays, which can provide high sensitivity and specificity in detecting subtle CNAs. In

addition, we used 58 paired tumor and adjacent nontumor tissues from the same individuals, which allowed us to identify highly recurrent CNAs other than accidental CNAs in HCC. Chromosomal instability, including copy number gains or losses in genomic DNA, is commonly observed in HCC, and several aberrant chromosomal loci have been frequently reported in association with this disease.32 For example, a gain at 1q is one of the most frequently detected alterations in HCC (58%-86%) and has been suggested as an early genomic event in the process of HCC development, whereas a loss at 8p is well documented in HCC, with a frequency of 29% to 77%.14 However, there is little doubt that additional CNAs and targeted genes within these loci exist in HCC. In this study we identified a total of 1,241 significant regions of CNAs.