PMID- 28005970
OWN - NLM
STAT- MEDLINE
DCOM- 20170728
LR  - 20211204
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 12
DP  - 2016
TI  - Phosphorylated Mammalian Target of Rapamycin p-mTOR Is a Favorable Prognostic 
      Factor than mTOR in Gastric Cancer.
PG  - e0168085
LID - 10.1371/journal.pone.0168085 [doi]
LID - e0168085
AB  - AIMS: The mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) 
      occurring downstream in the PI3K/Akt/mTOR pathway, are regarded as potential 
      prognostic markers for gastric cancer (GC). However, the prognostic value of 
      mTOR/p-mTOR expression remains controversial. In this study, we determined the 
      expression of mTOR, p-mTOR, p70S6k, and p-p70S6K in GC, and investigated the 
      correlation between their overexpression, clinicopathological parameters, and 
      overall survival (OS). METHODS: The expression of mTOR, p-mTOR, p70S6k, and 
      p-p70S6K was examined in 120 GC patients by immunohistochemistry (IHC). The 
      association of protein expression with clinicopathological features and OS was 
      explored. The p-mTOR expression was detected in normal, adjacent, and GC tissues 
      using Western blot. Eligible studies retrieved from PubMed, Ovid, Web of Science 
      and Cochrane databases, were reviewed in this meta-analysis. RESULTS: IHC showed 
      that the rates of expression of the signal transduction molecules mTOR, p-mTOR, 
      p70S6k and p-p70S6K in GC were 60.8%, 54.2%, 53.3% and 53.3%, respectively. 
      Overexpression of mTOR and p70S6K showed no significant association with clinical 
      variables. Expression of p-mTOR was significantly associated with differentiation 
      (P < 0.01), depth of invasion (P < 0.01), lymph node metastasis (P = 0.04) and 
      TNM stage (P = 0.02). Expression of p-p70S6K was associated with differentiation 
      (P = 0.006), depth of invasion (P < 0.001), and TNM stage (P = 0.02). In survival 
      analysis, differentiation, depth of invasion, lymph node metastasis and TNM stage 
      were not related to OS (all P > 0.05). Furthermore, p-mTOR and p-p70S6K 
      expression, but not mTOR and p70S6K, were tightly associated with OS of GC 
      patients (P = 0.006 and P < 0.001, respectively). In Western blot, p-mTOR was 
      significantly higher in GC tissues than in normal and adjacent tissues. In the 
      present meta-analysis, mTOR overexpression showed no relationship with any 
      clinicopathological variables. However, p-mTOR was correlated with depth of 
      invasion, and TNM stage (all P < 0.05), and its overexpression was associated 
      with a shorter survival time (P < 0.001). CONCLUSION: The results suggest that 
      p-mTOR is a more valuable prognostic factor than mTOR in GC.
FAU - Cao, Guo-Dong
AU  - Cao GD
AD  - Anhui Medical University, Hefei, Anhui, China.
FAU - Xu, Xing-Yu
AU  - Xu XY
AD  - Anhui Medical University, Hefei, Anhui, China.
FAU - Zhang, Jia-Wei
AU  - Zhang JW
AD  - Department of General Surgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, China.
FAU - Chen, Bo
AU  - Chen B
AD  - Department of General Surgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, China.
FAU - Xiong, Mao-Ming
AU  - Xiong MM
AD  - Department of General Surgery, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, China.
LA  - eng
PT  - Journal Article
DEP - 20161222
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Biomarkers, Tumor/*metabolism
MH  - Combined Modality Therapy
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Neoplasm Staging
MH  - Phosphorylation
MH  - Prognosis
MH  - Signal Transduction
MH  - Stomach Neoplasms/metabolism/*pathology/therapy
MH  - Survival Rate
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC5179011
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/12/23 06:00
MHDA- 2017/07/29 06:00
PMCR- 2016/12/22
CRDT- 2016/12/23 06:00
PHST- 2016/07/01 00:00 [received]
PHST- 2016/11/20 00:00 [accepted]
PHST- 2016/12/23 06:00 [entrez]
PHST- 2016/12/23 06:00 [pubmed]
PHST- 2017/07/29 06:00 [medline]
PHST- 2016/12/22 00:00 [pmc-release]
AID - PONE-D-16-26266 [pii]
AID - 10.1371/journal.pone.0168085 [doi]
PST - epublish
SO  - PLoS One. 2016 Dec 22;11(12):e0168085. doi: 10.1371/journal.pone.0168085. 
      eCollection 2016.