Zhou Li, Yuan Da, Zhang Zhi-Gang, Liang Zhi-Yong, Zhou Wei-Xun, Yang Jian-Yu, Jiang Shu-Heng, Lu Jun, Zhang Tai-Ping, You Lei, Guo Jun-Chao, Zhao Yu-Pei
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100730, China.
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200240, China.
Cancer Lett. 2017 Jun 1;395:45-52. doi: 10.1016/j.canlet.2017.02.036. Epub 2017 Mar 7.
Thus far, clinicopathologic and prognostic significance of mTOR signaling pathway in pancreatic ductal adenocarcinoma (PDAC) remains unclear, although it is involved in PDAC. In this study, total (t-) and phosphorylated (p-) mTOR, 4EBP1 and P70S6K, were investigated. It was found that most aforementioned proteins were related to malignant and progressive phenotypes, especially histological grade, in independent development and validation cohorts of PDAC. In the development cohort, high expression and/or phosphorylation of mTOR, 4EBP1 and P70S6K were all univariately associated with poor tumor-specific survival, whereas p-mTOR, p-4EBP1 and p-P70S6K, adjusted for clinicopathologic variables, unlike t-mTOR, t-4EBP1 and t-P70S6K, were shown to be independent prognostic factors in multivariate analysis. Interestingly and importantly, the independently significant impacts of p-mTOR and p-4EBP1 on tumor-specific survival were confirmed in the validation cohort. Contrarily, t-mTOR and t-4EBP1 were only univariately significant, while t-P70S6K and p-P70S6K were not prognostic. Finally, mTOR and EIF4EBP1, genes encoding mTOR and 4EBP1, also serve as prognostic indicators in the publicly available TCGA RNA-sequencing database. Our data indicate that expression and activation, especially the latter, of mTOR and 4EBP1, might have clinicopathologic and prognostic significance in PDAC.
迄今为止，尽管mTOR信号通路参与了胰腺导管腺癌（PDAC）的发生发展，但其临床病理及预后意义仍不明确。在本研究中，对总（t-）mTOR、磷酸化（p-）mTOR、4EBP1和P70S6K进行了研究。结果发现，在PDAC的独立开发和验证队列中，上述大多数蛋白与恶性和进展性表型相关，尤其是组织学分级。在开发队列中，mTOR、4EBP1和P70S6K的高表达和/或磷酸化均与较差的肿瘤特异性生存率单因素相关，而在多因素分析中，经临床病理变量校正后的p-mTOR、p-4EBP1和p-P70S6K，与t-mTOR、t-4EBP1和t-P70S6K不同，显示为独立的预后因素。有趣且重要的是，在验证队列中证实了p-mTOR和p-4EBP1对肿瘤特异性生存的独立显著影响。相反，t-mTOR和t-4EBP1仅单因素显著，而t-P70S6K和p-P70S6K无预后意义。最后，编码mTOR和4EBP1的基因mTOR和EIF4EBP1，在公开可用的TCGA RNA测序数据库中也作为预后指标。我们的数据表明，mTOR和4EBP1的表达和激活，尤其是后者，可能在PDAC中具有临床病理及预后意义。
