Clinicopathological characteristics of TERT promoter mutation and telomere length in hepatocellular carcinoma

Abstract

Promoter mutations in telomerase reverse transcriptase (TERT) and telomere length have been studied in various tumors. In the present study, the frequency and clinical characteristics of TERT promoter mutation and telomere length were studied in hepatocellular carcinoma (HCC). TERT promoter mutation and telomere length were analyzed in 162 tumor samples of the patients with HCC by sequencing and real-time PCR, respectively. The TERT promoter mutation rate was 28.8% (46/160) in HCC and was associated with males (P = 0.027). The telomere length was not significantly different in the presence of a TERT promoter mutation but was shorter in high-grade tumor stages (P = 0.048). Survival analyses showed that poor overall survival was associated with longer telomere length (P = 0.013). However, the TERT promoter mutation did not have a prognostic value for HCC. Multivariate survival analyses demonstrated that the telomere length was an independent prognostic marker for poor overall survival (hazard ratio = 1.75, 95% confidence interval: 1.046–2.913, P = 0.033). These data demonstrated that TERT promoter mutation is a frequent event in HCC; however, telomere length, but not the presence of a TERT promoter mutation, might have potential value as a prognostic indicator of HCC.

<em>TERT-CLPTM1</em> locus polymorphism (rs401681) is associated with the prognosis of hepatocellular carcinoma

“…However, we found no evidence that SNP rs401681 is associated with mean TL or TERT mutation. In our previous study, we found that ALT level and TL were significantly related 9. But in this study, aspartate transaminase and ALT were not associated with TERT -CLPTM1 locus polymorphism.…”

“…Also, TL might have a potential value as a prognostic factor in HCC. According to many reports, while shortened tumor TL shows poorer prognosis in most solid tumors, HCC has been observed with favorable prognosis as in colorectal cancer 1,9…”

Androgen Receptor Enhances Hepatic Telomerase Reverse Transcriptase Gene Transcription After Hepatitis B Virus Integration or Point Mutation in Promoter Region

“…The results showed HBV integrations in 24%-30% of male patients with HCC but only in 12%-17% of female patients with HCC (20)(21)(22) ; -124A>G TERT promoter mutation was identified in 32%-33% of male patients with HCC but only in 15%-24% in female patients with HCC. (23,24) Though the sample size of female patients with HCC included in these studies was usually small (fewer than 10 cases), the results did support an enrichment of HBV insertions and TERT promoter mutations in male patients with HCC. Therefore, a mechanism for such genetic changes might exist to induce TERT expression predominantly in hepatocytes from male, but not female, patients.…”

Non-Alcoholic Steatohepatitis, Liver Cirrhosis and Hepatocellular Carcinoma: The Molecular Pathways

“…Interestingly, shorter telomeres are observed more frequently (telomere length ratio between HCC and surrounding tissues lower than the mean, 70.1% versus higher, 29.9%) in HCC that is not related to hepatitis B (50.0% versus 50.0%) or C (60.0% versus 40.0%), or alcohol abuse (50.0% versus 50.0%), although the difference does not reach statistical significance [83]. Telomere shortening can be detected in peripheral blood.…”

“…Early liver carcinogenesis is associated with telomere shortening, while disease progression is associated with telomere extension, cell immortalisation and reactivation of telomerase [83]. Longer telomeres in HCC are associated with higher stage (regional or distant spread versus localised tumour) and grade (III-IV versus lower grade) as well as with worse survival [83,84]. Telomerase promotes HCC development via several pathways, not limited to maintenance of telomeres and thus cellular proliferation.…”