Telomere deregulation at the late stage of alcohol-associated hepatocarcinogenesis When compared to their peritumoral cirrhotic tissue samples, alcohol-associated HCC expressed higher levels of the Ki67 proliferative marker (8% versus 1%) but the difference was not statistically significant. Figure 1A shows that TA, hTERT and hTR expressions were augmented in alcohol-associated

HCC but these differences were not statistically significant. Table 3 shows that the pattern of shelterin and non-shelterin genes expression was not significantly different between alcohol-associated FHPI molecular weight HCC and alcohol-associated cirrhosis. Western-blot analysis confirmed the qRTPCR results (Figure 2C and D). These results suggested that at the telomere level, there is no significant deregulation that distinguishes alcohol-associated HCC from alcohol-associated cirrhosis. Discussion The data suggest that the development of HCC involves

the accumulation of numerous telomere dysfunctions that appear to include cause-specific deregulations. Our sample collection permitted the comparison Selleck Mocetinostat of histologically non-cirrhotic livers with cirrhosis and HCC in the context of HBV and HCV infections, and alcohol exposure. Given that HCC mostly develop from cirrhotic livers, we assumed that comparing histologically non-cirrhotic liver samples with cirrhotic liver samples would reflect early carcinogenesis whereas comparing cirrhotic liver samples with tumor samples would reflect later carcinogenic events. Indeed, alterations in TRF length, TA, hTERT and hTR expression were identified at both the early and late steps of hepatocarcinogenesis. These Farnesyltransferase alterations were observed roughly in parallel among the 3 different causes of HCC. In contrast, the numerous changes demonstrated in the expression of telomere protective factors appeared to be restricted to early hepatocarcinogenesis. Additionally, these changes permitted the identification of a gene expression signature for each cause of cirrhosis

and HCC. There was furthermore, evidence that the telomere phenotype of HBV-associated-cirrhosis and HCC was different from that of the other causes of cirrhosis and HCC. No correlation was found between TA, hTERT expression and telomere length with respect to the cause of cirrhosis and HCC. This result is in agreement with the study of Saini et al. who compared TA, TRF and hTERT expression between HBV, HCV, and non-B non-C-related HCC [34]. In contrast, Guo et al. reported that HbsAg positive HCC expressed higher amounts of hTERT mRNA than HbsAg MI-503 negative HCC [35]. Whatever the cause, there was no significant difference in TRF length between cirrhotic and non-cirrhotic samples.