In contrast, the tumor samples VX-680 ic50 expressed higher levels of the Ki67 proliferative marker and contained shorter telomeres than either non-cirrhotic or cirrhotic samples. There was no precise correlation find more between the level of hTERT expression measured by qRTPCR and the level of TA measured by the quantitative TRAP assay, suggesting that posttranscriptional modifications might participate to modulate TA during hepatocarcinogenesis. Additionally, there was no significant correlation between either hTERT expression or TA and telomere length. Conversely, Figure 1A shows that the shorter were the telomeres in sample sets, the higher were TA and hTERT expression in these samples. This conflicting data might be explained,
at least in part, by changes in regulating access of the telomere to the telomerase in liver cells, i.e. by changes in telomere proteins content. Accumulating evidence suggests that telomeric factors dysregulation is involved in cancer development as has been demonstrated in the maintenance of the tumor phenotype. To our knowledge, this study is the first which investigates the expression of the main telomere protective genes learn more in the main subtype of cirrhosis and HCC. Previously, Oh et al. demonstrated that expression of TRF1, TRF2 and TIN2 was gradually increased according to the progression of hepatocarcinogenesis in HBsAg positive individuals . In this study, HBV-, HCV- and alcohol-associated
cirrhosis displayed significantly different distinct patterns of telomere protective factor expression, as compared with that of non-cirrhotic liver (Table 2). The 3 subtypes of cirrhosis possessed a specific
signature, with respect to telomere protective factor expression (Additional file 3: Table S3). Although the expression level of all the shelterin and non-shelterin telomere factors was not equally distributed between the 3 causes of cirrhosis (Additional file 3: Table S3), the telomere phenotype of HBV-associated-cirrhosis appeared different from that of the 2 other causes of the cirrhosis. When compared with non-cirrhotic liver, HBV-associated cirrhosis displayed a dramatic repression of all shelterin and non-shelterin factors except HMRE11A and RAD50. In contrast, the alterations in telomere factor expression between non-cirrhotic and cirrhotic samples were similar between HCV- and alcohol-associated cirrhosis. Accordingly, the expression pattern of all telomere factors, except TIN2 and HMRE11B, was identical between HCV- and alcohol-associated cirrhosis (Additional file 3: Table S3). These results suggest that cause-specific factors are involved in initiating telomere dysfunction in the liver. For example, HBV-associated cirrhosis displayed very low amounts of TRF2 that has been demonstrated to elicit telomere shortening ex vivo. Whatever the cause, the levels of shelterin and non-shelterin telomere factors expression were not significantly different between cirrhotic and HCC samples (Figure 1B and Table 3).