Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma
Influence of Rictor and Raptor Expression of mTOR Signaling on Long-Term Outcomes of Patients with Hepatocellular Carcinoma
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DOI：
10.1007/s10620-014-3417-7
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发表时间：
2015-04-01
影响因子：
3.1
通讯作者：
Kon, Masanori
中科院分区：
文献类型：
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作者：
Kaibori, Masaki;Shikata, Nobuaki;Kon, Masanori
背景雷帕霉素靶蛋白（mTOR）介导的异常信号在肝细胞癌（HCC）中发生频率很高，表明mTOR是靶向治疗的候选者。mTOR形成两种复合物，称为mTORC 1（mTOR与raptor复合）和mTORC 2（mTOR与rictor复合）。有小的研究mTORC 1和mTORC 2的表达动力学HCC。方法我们研究了62例HCC患者接受根治性切除术。我们使用单变量和多变量分析来确定可能影响肝切除术后疾病和总生存率的因素。结果/结论rictor和raptor mRNA在肿瘤组织中的高表达率可作为无病生存的独立预后指标。术前血清白蛋白和肿瘤中mTOR mRNA的低水平和高水平分别被确定为总生存率的独立指标。在癌组织中具有高水平mTOR和rictor mRNA以及高rictor/raptor比率的患者中，HCC可能在肝切除术后早期复发。我们的结论是，癌组织中mTOR表达的分析是预测肝癌根治性治疗后复发的一个重要策略。
Background Aberrant signaling mediated by the mammalian target of rapamycin (mTOR) occurs at high frequency in hepatocellular carcinoma (HCC), indicating that mTOR is a candidate for targeted therapy. mTOR forms two complexes called mTORC1 (mTOR complexed with raptor) and mTORC2 (mTOR complexed with rictor). There are minor studies of the expression kinetics of mTORC1 and mTORC2 in HCC.Methods We studied 62 patients with HCC who underwent curative resection. We used univariate and multivariate analyses to identify factors that potentially influence disease and overall survival after hepatectomy. The mRNA and protein levels of mTOR, rictor and raptor in cancer and non-cancer tissues were analyzed using quantitative RTPCR, immunohistochemistry and Western blotting.Results/Conclusion High ratio of the levels of rictor and raptor mRNAs in tumors was identified as independent prognostic indicators for disease-free survival. Low and high levels of preoperative serum albumin and mTOR mRNA in the tumor, respectively, were identified as independent indicators of overall survival. HCC is likely to recur early after hepatic resection in patients with high levels of mTOR and rictor mRNAs and high rictor/raptor ratios in cancer tissues. We conclude that analysis of mTOR expression in cancer tissues represents an essential strategy to predict HCC recurrence after curative treatment.