PMID- 19223493 OWN - NLM STAT- MEDLINE DCOM- 20090414 LR - 20221207 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 15 IP - 5 DP - 2009 Mar 1 TI - Overexpression of phosphorylated mammalian target of rapamycin predicts lymph node metastasis and prognosis of chinese patients with gastric cancer. PG - 1821-9 LID - 10.1158/1078-0432.CCR-08-2138 [doi] AB - PURPOSE: 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. EXPERIMENTAL DESIGN: 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. FAU - Yu, Guanzhen AU - Yu G AD - Department of Medical Oncology, Changzheng Hospital, Shanghai, People's Republic of China. FAU - Wang, Jiejun AU - Wang J FAU - Chen, Ying AU - Chen Y FAU - Wang, Xi AU - Wang X FAU - Pan, Jun AU - Pan J FAU - Li, Gang AU - Li G FAU - Jia, Zhiliang AU - Jia Z FAU - Li, Qiang AU - Li Q FAU - Yao, James C AU - Yao JC FAU - Xie, Keping AU - Xie K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090217 PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.1.1 (mTOR protein, mouse) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Adenocarcinoma/*metabolism/secondary MH - Adenocarcinoma, Mucinous/*metabolism/secondary MH - Animals MH - Asian People MH - Blotting, Western MH - Carcinoma, Papillary/*metabolism/secondary MH - Carcinoma, Signet Ring Cell/*metabolism/secondary MH - Cells, Cultured MH - Endothelium, Vascular MH - Female MH - Humans MH - Immunoenzyme Techniques MH - Liver Neoplasms/*metabolism/secondary MH - Lymphatic Metastasis MH - Male MH - Mice MH - Mice, Nude MH - Middle Aged MH - Neoplasm Staging MH - Neovascularization, Pathologic MH - Phosphorylation MH - Prognosis MH - Protein Kinases/*metabolism MH - Stomach Neoplasms/*metabolism/pathology MH - Survival Rate MH - TOR Serine-Threonine Kinases MH - Tissue Array Analysis MH - Vascular Endothelial Growth Factor A/metabolism MH - Xenograft Model Antitumor Assays EDAT- 2009/02/19 09:00 MHDA- 2009/04/15 09:00 CRDT- 2009/02/19 09:00 PHST- 2009/02/19 09:00 [entrez] PHST- 2009/02/19 09:00 [pubmed] PHST- 2009/04/15 09:00 [medline] AID - 1078-0432.CCR-08-2138 [pii] AID - 10.1158/1078-0432.CCR-08-2138 [doi] PST - ppublish SO - Clin Cancer Res. 2009 Mar 1;15(5):1821-9. doi: 10.1158/1078-0432.CCR-08-2138. Epub 2009 Feb 17.