PMID- 21387259
OWN - NLM
STAT- MEDLINE
DCOM- 20110926
LR  - 20211203
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 117
IP  - 16
DP  - 2011 Aug 15
TI  - Activation of mammalian target of rapamycin pathway confers adverse outcome in 
      nonsmall cell lung carcinoma.
PG  - 3763-73
LID - 10.1002/cncr.25959 [doi]
AB  - BACKGROUND: Dysregulation of the mammalian target of rapamycin (mTOR) pathway has 
      been shown to contribute to tumorigenesis. This study explored protein expression 
      profiles of mTOR pathway and the relationship with prognosis in patients with 
      nonsmall cell lung carcinoma (NSCLC). METHODS: The protein expression profiles of 
      mTOR/phosphorylated (p-)mTOR, phosphoinositide-dependent kinase 1 (PDK1)/p-PDK1, 
      p-Akt1, and P70 ribosomal protein S6 kinase (P70S6K)/p-P70S6K were determined via 
      immunohistochemical staining assay. The clinical prognostic values of both single 
      and combined protein expression were investigated with univariate and 
      multivariate survival analysis. RESULTS: Compared with normal lung tissues, the 
      protein levels of mTOR/p-mTOR, p-Akt1 Ser473/Thr308, and P70S6K/p-P70S6K were 
      higher (all P < .05), whereas p-PDK1 was lower (P < .05) in tumor tissues. p-mTOR 
      expression was associated with histological differentiation, histological type, 
      lymph node invasion, and stage (all P < .05). Overall survival in NSCLC patients 
      was significantly shorter in cases with positive phenotype for p-mTOR, p-PDK1, 
      and p-P70S6K (all P < .05). Subjects with coexpression of any 2 of p-mTOR, 
      p-PDK1, p-Akt1 Ser473, and p-P70S6K demonstrated worse prognosis than those 
      expressing no biomarker or any 1 biomarker alone (all P < .05). Multivariate 
      analysis showed that the combination of p-mTOR/p-P70S6K is an independent 
      prognostic factor in addition to tumor stage. CONCLUSIONS: This study provides 
      clinical evidence that activated components of mTOR pathway, not total protein, 
      are predictors of poor prognosis in NSCLC. Moreover, evaluating 
      protein-expression profiles of these molecules might be a new strategy for 
      individual therapy in subjects with NSCLC.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Liu, Dan
AU  - Liu D
AD  - Department of Respiratory Medicine, West China Hospital, Sichuan University, 
      Chengdu, China.
FAU - Huang, Yi
AU  - Huang Y
FAU - Chen, Bojiang
AU  - Chen B
FAU - Zeng, Jing
AU  - Zeng J
FAU - Guo, Na
AU  - Guo N
FAU - Zhang, Shangfu
AU  - Zhang S
FAU - Liu, Lunxu
AU  - Liu L
FAU - Xu, Hong
AU  - Xu H
FAU - Mo, Xianming
AU  - Mo X
FAU - Li, Weimin
AU  - Li W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110308
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - EC 2.7.- (Phosphotransferases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism/mortality
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*metabolism/mortality
MH  - Male
MH  - Middle Aged
MH  - Phosphorylation
MH  - Phosphotransferases/metabolism
MH  - Prognosis
MH  - Protein Array Analysis
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2011/03/10 06:00
MHDA- 2011/09/29 06:00
CRDT- 2011/03/10 06:00
PHST- 2010/09/10 00:00 [received]
PHST- 2010/12/31 00:00 [revised]
PHST- 2011/01/03 00:00 [accepted]
PHST- 2011/03/10 06:00 [entrez]
PHST- 2011/03/10 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
AID - 10.1002/cncr.25959 [doi]
PST - ppublish
SO  - Cancer. 2011 Aug 15;117(16):3763-73. doi: 10.1002/cncr.25959. Epub 2011 Mar 8.