The impact of SIRT1 serum level and its gene single nucleotide polymorphism (rs7895833) on the prediction of hepatocellular carcinoma in a cohort of cirrhotic population.

Abstract

Background: SIRT1 role in cancer and specifically in HCC remains controversial. Depending on the tissue and the context, SIRT1 has so far been found to have oncogenic as well as tumor suppressive functions.

Objectives: The present work was designed to evaluate the role of serum SIRT1 as a possible biomarker for the diagnosis of HCC, the effect of SIRT1 single nucleotide polymorphism (SNP) on SIRT1 serum levels and its potential role in the development and progression of HCC.

Methods: Seventy patients with cirrhosis [40 with HCC and 30 without HCC] and 30 healthy controls were enrolled in the study. Serum level of SIRT1 was measured by ELISA and genotyping for SIRT1 SNP (rs7895833) was performed using TaqMan SNP Genotyping Assay.

Results: Serum SIRT1 levels in HCC patients were significantly lower than in cirrhotic patients without HCC and controls (P<0.001) and were inversely correlated with Child-Pugh score and HCC size and stage (P<0.01). ROC curve analysis revealed that serum SIRT1 was superior to serum alpha fetoprotein in the detection of HCC (AUC= 0.985 vs. 0.860). SIRT1 serum levels were significantly lower in subjects with heterozygous (A/G) variant than in those with homozygous (A/A) allele 1 (P=0.002). The mutant allele (G) was more prevalent among HCC patients than among controls.

Conclusion: Decreased SIRT1 level may play a role in the development and progression of HCC. Serum SIRT1 could be a promising biomarker for detection of HCC among cirrhotic patients and could be a potential therapeutic candidate.