Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma
Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma
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DOI：
10.1158/1078-0432.ccr-07-0738
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发表时间：
2007-08-15
影响因子：
11.5
通讯作者：
Filipits, Martin
中科院分区：
文献类型：
--
作者：
Herberger, Beata;Puhalla, Harald;Filipits, Martin
目的：哺乳动物雷帕霉素靶蛋白（mTOR）是一种在细胞生长和稳态中起关键作用的蛋白激酶。由于其调节在肿瘤中经常改变，mTOR目前正在研究作为抗癌治疗的潜在靶点。我们研究的目的是确定活化的mTOR（p-mTOR）在胆道腺癌（BTA）患者的预后价值，以加强BTA使用mTOR inhibitors.Experimental Design的靶向治疗的理由：我们确定了磷酸化mTOR的单克隆抗体的免疫组化的石蜡包埋的BTA手术标本中的p-mTOR的表达。总生存率进行了分析与考克斯模型调整的临床和病理factors.Results：p-mTOR免疫染色阳性56至88（64%）肿瘤。激活的mTOR与患者的任何临床或病理变量无关，但可预测患者的总生存期。与p-mTOR阴性肿瘤患者相比，p-mTOR阳性肿瘤患者的总生存期显著缩短（死亡风险比为2.57; 95%置信区间为1.35-4.89; P=0.004）。多变量考克斯比例风险回归分析确定p-mTOR是死亡的独立预后因素（死亡的校正风险比，2.44; 95%可信区间，1.24-4.80; P=0.01）。BTA和p-mTOR阳性肿瘤患者的总生存期明显短于p-mTOR阳性患者阴性肿瘤，并可能在未来受益于mTOR抑制剂的靶向治疗。
Purpose: The mammalian target of rapamycin (mTOR) is a protein kinase that plays a key role in cellular growth and homeostasis. Because its regulation is frequently altered in tumors, mTOR is currently under investigation as a potential target for anticancer therapy. The purpose of our study was to determine the prognostic value of activated mTOR (p-mTOR) in patients with biliary tract adenocarcinoma (BTA), in order to strengthen the rationale for targeted therapy of BTA using mTOR inhibitors.Experimental Design: We determined expression of p-mTOR in paraffin-embedded surgical specimens of BTA by immunohistochemistry with a monoclonal antibody to phosphorylated mTOR. Overall survival was analyzed with a Cox model adjusted for clinical and pathologic factors.Results: Immunostaining for p-mTOR was positive in 56 to 88 (64%) tumors. Activated mTOR was not associated with any of the clinical or pathologic variables of the patients but predicted overall survival of the patients. Overall survival was significantly shorter in patients with p-mTOR-positive tumors as compared with patients with p-mTOR-negative tumors (hazard ratio for death 2.57; 95% confidence interval, 1.35-4.89; P=0.004). Multivariate Cox proportional hazards regression analyses identified p-mTOR to be an independent prognostic factor for death (adjusted hazard ratio for death, 2.44; 95% confidence interval, 1.24-4.80; P=0.01).Conclusions: Patients with BTA and p-mTOR-positive tumors have a significantly shorter overall survival than patients with p-mTOR-negative tumors and may benefit from targeted therapy with mTOR inhibitors in the future.