Data from Overexpression of Phosphorylated Mammalian Target of Rapamycin Predicts Lymph Node Metastasis and Prognosis of Chinese Patients with Gastric Cancer

Abstract

<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> 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.</p><p><b>Results:</b> 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, T<sub>1</sub>/T<sub>2</sub> 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.</p><p><b>Conclusions:</b> 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.</p></div>