| Objective: To investigate the frequency and type of mutations of IDH1 in IHCC,figure out the prognostic significance of mutant IDH1 in patients with IHCC and analyze the correlation between IDH1 status and clinic-pathologic characteristics in IHCC.Methods: IDH1 status was detected by Sanger sequencing in 85 tumor samples from IHCC patients undergoing surgery from 2009 to 2014 in Hepatic Surgery Centre,Tongji Hospital.Postsurgical survival and recurrence of patients were followed up.Clinic-pathologic features were collected and analyzed.Expression of ki-67 was determined by immunohistochemistry.Results: IDH1 mutation was found in 15% IHCC tumor samples.Compared with wild type,patients with mutant IDH1 had a higher overall survival rate and a lower recurrence rate.IDH1 mutation was correlated with smaller tumor size,lower CA19-9 level and lower TNM stage.Ki-67 staining was lower in IHCC tumors with mutant IDH1.Conclusions: IDH1 mutation confers a beneficial prognosis and correlates with less aggressive clinic-pathologic characteristics in patients with IHCC.Objective: To investigate the function of mutant IDH1 in IHCC tumor growth,figure out the potential mechanism by which mutant IDH1 influences tumor growth.Methods: Role of mutant IDH1 in IHCC tumor growth was measured by cell proliferation assay,colony formation assay in soft agar,cell cycle analysis and xenograft tumor models.Akt,ERK,p38 MAPK,and JNK signaling which commonly affect tumor growth were tested by western blotting to explore the potential mechanism.Results: Mutant IDH1 exhibited a growth-inhibitory effect in IHCC cell lines in vitro and in vivo.Akt signaling was suppressed in IHCC cell lines expressing a mutant IDH1.Reactivation of Akt signaling by SC79 promoted the inhibited growth of cell lines expressing a mutant IDH1 in IHCC.Conclusions: Mutant IDH1 confers growth-inhibitory effect by suppressing Akt signaling in IHCC. |
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