Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Down-regulation of sirtuin 3 is associated with poor prognosis in hepatocellular carcinoma after resection

Jia-Xing Wang1, Yong Yi1, Yi-Wei Li1, Xiao-Yan Cai1, Hong-Wei He1, Xiao-Chun Ni1, Jian Zhou1, Yun-Feng Cheng2, Jian-Jun Jin2, Jia Fan1 and Shuang-Jian Qiu12*

Author Affiliations

1 Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, The Chinese Ministry of Education, Shanghai, People’s Republic of China

2 Biomedical Research Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

For all author emails, please log on.

BMC Cancer 2014, 14:297  doi:10.1186/1471-2407-14-297

Published: 28 April 2014

Abstract

Background

Sirtuin 3 (Sirt3), one of the seven Sirtuins family members, plays critical roles in the progression of multiple cancer types. However, its role in the prognosis of hepatocellular carcinoma (HCC) has not yet been investigated systematically.

Methods

The correlation of Sirtuins expression with prognosis of HCC was determined by immunohistochemistry (IHC) in a large HCC patient cohort (n = 342). Expression of Sirt3 in tumoral and peritumoral tissues of HCC patients were further determined by western blotting (WB).

Results

IHC and WB studies both showed a decreased expression of Sirt3 in tumoral tissues compared with peritumoral tissues (P = 0.003 for IHC, P = 0.0042 for WB). Decreased expression of Sirt3 in both tumoral and peritumoral tissues was associated with increased recurrence probability and decreased overall survival rate by univariate analyses (intratumoral Sirt3: P = 0.011 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.017 for TTR, P = 0.023 for OS), the prognostic value was strengthened by multivariate analyses (intratumoral Sirt3: P = 0.031 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.047 for TTR, P = 0.031 for OS). Intratumoral Sirt3 also showed a favorable prognostic value in patients with BCLC stage A (TTR, P = 0.011; OS, P < 0.001). In addition, we found that IHC studies of other sirtuin members showed a decreased expression of Sirt2, Sirt4 and Sirt5 and an increased expression of Sirt1, Sirt6 and Sirt7 in intratumoral tissues compared with peritumoral tissues. In contrast to Sirt3, other members did not showed a remarkable correlation with HCC prognosis.

Conclusions

Down-regulation of intratumoral and peritumoral Sirt3 were both associated with poor outcome in HCC, moreover, intratumoral Sirt3 was a favorable prognostic predictor in early stage patients.

Keywords:
Sirtuin; Hepatocellular carcinoma; Prognosis