Expression And Prognostic Significance Of MTOR And P-mTOR In Gastric Cancer

Aims: The mammalian target of rapamycin(mTOR)and phosphorylated mTOR(p-mTOR)occurring downstreamin 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,p70S6 k,and p-p70S6 K in GC,and investigated the correlation between their overexpression,clinicopathological parameters,and overall survival(OS).Methods: The expression of mTOR,p-mTOR,p70S6 k,and p-p70S6 K 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 fromPub Med,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,p70S6 k and p-p70S6 K in GC were 60.8%,54.2%,53.3% and 53.3%,respectively.Overexpression of mTOR and p70S6 K 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-p70S6 K 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-p70S6 K expression,but not mTOR andp70S6K,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.