Overexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of chinese patients with gastric cancer.
OBJECTIVE
We determined the expression of mammalian target of rapamycin (mTOR) and its activated form, p-mTOR, in Chinese patients with gastric cancer and its clinical effects and underlying mechanisms.


METHODS
Tissue microarray blocks containing gastric cancer tissue and matched noncancer gastric tissue specimens obtained from 1,072 patients were constructed. Expression of total mTOR and p-mTOR in these specimens was analyzed using immunohistochemical studies and confirmed by Western blotting.


RESULTS
The overall rates of total mTOR and p-mTOR overexpression were 50.8% (545 of 1,072) and 46.5% (499 of 1,072), respectively. The p-mTOR overexpression was significantly correlated with total mTOR overexpression. Overexpression of total mTOR protein was significantly correlated with tumor differentiation, T1/T2 tumors, and stage I/II/III disease, whereas p-mTOR overexpression was significantly correlated with lymph node metastasis and all stage disease. The Cox proportional hazards model revealed that the overexpression of p-mTOR, but not total mTOR, was an independent prognostic factor for gastric cancer. The overexpression of p-mTOR also predicted the angiogenic phenotype of human gastric cancer and regulated angiogenesis of gastric cancer cells.


CONCLUSIONS
Increased activation of mTOR is frequent in human gastric cancer and overexpression of p-mTOR is an independent prognostic factor, suggesting that mTOR pathway could be a potential target for therapy of this malignancy.
Yu
Guanzhen
G
Department of Medical Oncology, Changzheng Hospital, Shanghai, People's Republic of China.
Wang
Jiejun
J
Chen
Ying
Y
Wang
Xi
X
Pan
Jun
J
Li
Gang
G
Jia
Zhiliang
Z
Li
Qiang
Q
Yao
James C
JC
Xie
Keping
K
D000230:Adenocarcinoma / Q000378:metabolism* / Q000556:secondary; D002288:Adenocarcinoma, Mucinous / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D044466:Asian People; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000556:secondary; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism* / Q000556:secondary; D002478:Cells, Cultured; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases