title: Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma.
abstract: BACKGROUND
  Aberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC.
  
  
  METHODS
  We studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RT-PCR, immunohistochemistry and Western blotting.
  
  
  CONCLUSIONS
  High ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.
authors.affiliation: Department of Surgery, Hirakata Hospital, Kansai Medical University, 2-5-1 Shinmachi, Hirakata, Osaka, 573-1191, Japan, kaibori@hirakata.kmu.ac.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kaibori
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shikata
authors.forename: Tatsuma
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Morihiko
authors.initials: M
authors.lastname: Ishizaki
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsui
authors.forename: Hiroya
authors.initials: H
authors.lastname: Iida
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Miki
authors.forename: Richi
authors.initials: R
authors.lastname: Nakatake
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Okumura
authors.forename: Katsuji
authors.initials: K
authors.lastname: Tokuhara
authors.forename: Kentaro
authors.initials: K
authors.lastname: Inoue
authors.forename: Jouji
authors.initials: J
authors.lastname: Wada
authors.forename: Michio
authors.initials: M
authors.lastname: Oda
authors.forename: Mikio
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Masanori
authors.initials: M
authors.lastname: Kon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D002352:Carrier Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C492571:RICTOR protein, human; D012333:RNA, Messenger; C463659:RPTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D000076223:Regulatory-Associated Protein of mTOR; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases