title: Clinical significance of PICT1 in patients of hepatocellular carcinoma with wild-type TP53.
abstract: BACKGROUND
  TP53 is one of the most widely known cancer suppressor genes. Mutations in TP53 are ubiquitously observed in almost all cancers. Incidences of mutations range from ~15-70 % in patients with hepatocellular carcinoma (HCC). Moreover, patients with mutated TP53 have poorer prognoses than those with wild-type TP53; therefore, it would be beneficial to predict the prognosis of HCC patients with wild-type TP53. We previously reported that PICT1, coding a nucleolus protein, regulates TP53 through indirect association.
  
  
  METHODS
  In this study, we examined PICT1 expression levels and the status of TP53 in 51 primary HCC tissues in order to determine the clinical significance of PICT1 expression and the function of PICT1 in HCC cells.
  
  
  RESULTS
  We detected 6 mutations in the 51 samples. In 45 patients with wild-type TP53, those with high PICT1 expression (n = 11) had poorer prognoses than those with low PICT1 expression (n = 34), and there were no significant associations with other clinicopathological factors. According to gene set enrichment analysis, PICT1 expression was inversely correlated with the gene set of TP53. In vitro assays indicated that suppression of PICT1 expression caused an increase in TP53 expression, reduction in cell proliferation, and arrest at the G1 phase of the cell cycle in HCC cells expressing wild-type TP53.
  
  
  CONCLUSIONS
  PICT1 should be a useful prognostic marker in HCC patients having wild-type TP53. Furthermore, PICT1 may become a promising therapeutic target because of its ability to increase the expression and activation of TP53.
authors.affiliation: Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita, Japan, mishibashi@beppu.kyushu-u.ac.jp.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Kogo
authors.forename: Kohei
authors.initials: K
authors.lastname: Shibata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ueo
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Uchi
authors.forename: Tae
authors.initials: T
authors.lastname: Matsumura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takano
authors.forename: Genta
authors.initials: G
authors.lastname: Sawada
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Kousuke
authors.initials: K
authors.lastname: Mima
authors.forename: Junji
authors.initials: J
authors.lastname: Kurashige
authors.forename: Sayuri
authors.initials: S
authors.lastname: Akiyoshi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwaya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Eguchi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Sudo
authors.forename: Keishi
authors.initials: K
authors.lastname: Sugimachi
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Go
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
mesh_terms: D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C500712:NOP53 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins