title: Phosphorylated Mammalian Target of Rapamycin p-mTOR Is a Favorable Prognostic Factor than mTOR in Gastric Cancer.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  The results suggest that p-mTOR is a more valuable prognostic factor than mTOR in GC.
authors.affiliation: Anhui Medical University, Hefei, Anhui, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Cao
authors.affiliation: Anhui Medical University, Hefei, Anhui, China.
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
authors.forename: Mao-Ming
authors.initials: MM
authors.lastname: Xiong
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases