Blood circulating C228T TERT gene promoter mutation is an independent factor for the prognosis of HBV–related hepatocellular carcinoma

Telomerase reverse transcriptase ( TERT ) promoter mutations are among the most common noncoding genetic lesions in various cancers, including hepatocellular carcinoma (HCC). The clinical and pathological implications of hepatitis B virus (HBV)–related HCC patients carrying promoter mutations are only partially resolved. A nested real–time PCR assay was optimized to detect C228T TERT gene promoter mutation (C228T) from plasma samples with a detection limit of 0.1%. The established assay was used to investigate the association of the C228T with the clinical presentation of HBV–related HCC patients. The C228T was detected only in the HCC group ( n = 40/159, 25.2%), not in the other control groups ( n = 0/160). The mutation rate was significantly higher in HCC patients with low albumin concentration, increased direct bilirubin, abdominal lymphadenopathy, and portal vein thrombosis, compared with HCC patients without these factors ( p < 0.05); the mutation rate also increased progressively with more advanced stages ( p < 0.05) and was significantly associated with shorter overall survival (OS). The C228T is associated with advanced stages, poorer liver function, and shorter overall survival; hence, it could be used as a novel biomarker for the prognosis of HBV–related HCC patients.