Down-regulation of sirtuin 3 is associated with poor prognosis in hepatocellular carcinoma after resection.
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.
Jia-Xing
JX
Wang
Yong
Y
Yi
Yi-Wei
YW
Li
Xiao-Yan
XY
Cai
Hong-Wei
HW
He
Xiao-Chun
XC
Ni
Jian
J
Zhou
Yun-Feng
YF
Cheng
Jian-Jun
JJ
Jin
Jia
J
Fan
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of China. qiu.shuangjian@zs-hospital.sh.cn.
Shuang-Jian
SJ
Qiu
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D056566:Sirtuin 3 / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate
C466093:SIRT3 protein, human; D056566:Sirtuin 3