Significance of Genetic Alterations and Telomere Length in Hepatocellular Carcinoma.

Telomerase reverse transcriptase () mutations are reportedly the most frequent somatic genetic alterations in hepatocellular carcinoma (HCC). An integrative analysis of -telomere signaling during hepatocarcinogenesis is lacking. This study aimed to investigate the clinicopathological association and prognostic value of gene alterations and telomere length in HCC patients undergoing hepatectomy as well as transarterial chemotherapy (TACE). promoter mutation, expression, and telomere length were analyzed by Sanger sequencing and real-time PCR in 305 tissue samples. Protein-protein interaction (PPI) analysis was performed to identify a set of genes that physically interact with . The PPI analysis identified eight key -interacting genes, namely , , , , , , , and . Among these, was the most strongly differentially expressed gene. promoter mutations were more frequent, expression was significantly higher, and telomere length was longer in tumors versus non-tumors. promoter mutations were most frequent in HCV-related HCCs and less frequent in HBV-related HCCs. promoter mutations were associated with higher levels and longer telomere length and were an independent predictor of worse overall survival after hepatectomy. expression was positively correlated with tumor differentiation and stage progression, and independently predicted shorter time to progression after TACE. The -telomere network may have a crucial role in the development and progression of HCC. -telomere abnormalities might serve as useful biomarkers for HCC, but the prognostic values may differ with tumor characteristics and treatment.