High expression of 5-hydroxymethylcytosine and isocitrate dehydrogenase 2 is associated with favorable prognosis after curative resection of hepatocellular carcinoma.
BACKGROUND
The expression of 5-hydroxymethylcytosine (5-hmC) and isocitrate dehydrogenase 2 (IDH2) is frequently downregulated in numerous cancers. 5-hmC and IDH2 expression in hepatocellular carcinoma (HCC) has yet to be determined.


METHODS
The immunohistochemical expression of 5-hmC and IDH2 were analyzed in tissue microarrays containing samples from 646 patients who had undergone hepatectomy for histologically proven HCC. The prognostic value of 5-hmC and IDH2 were evaluated by Cox regression and Kaplan-Meier analyses.


RESULTS
We discovered that low 5-hmC and IDH2 expression was associated with malignant behaviors. Low 5-hmC or IDH2 expression alone and combined 5-hmC and IDH2 expression were associated with lower overall survival (OS) rates and higher cumulative recurrence rates. Multivariate analysis indicated that 5-hmC or IDH2 and 5-hmC/IDH2 were independent prognostic indicators for OS and time to recurrence (TTR), which was confirmed in an independent validation cohort.


CONCLUSIONS
5-hmC and IDH2 correlate with less aggressive tumor behavior in HCC. When 5-hmC and IDH2 are considered together, they serve as a prognostic marker in patients with surgically resected HCCs.
Wei-Ren
WR
Liu
Meng-Xin
MX
Tian
Lei
L
Jin
Liu-Xiao
LX
Yang
Zhen-Bin
ZB
Ding
Ying-Hao
YH
Shen
Yuan-Fei
YF
Peng
Jian
J
Zhou
Shuang-Jian
SJ
Qiu
Zhi
Z
Dai
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai 200032, China. fan.jia@zs-hospital.sh.cn.
Jia
J
Fan
Ying-Hong
YH
Shi
D044503:5-Methylcytosine / Q000031:analogs & derivatives; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006498:Hepatectomy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000401:mortality / Q000517:prevention & control; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016896:Treatment Outcome
C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase