磷酸化雷帕霉素哺乳动物靶点p-mTOR在胃癌中是比mTOR更有利的预后因素。
Phosphorylated Mammalian Target of Rapamycin p-mTOR Is a Favorable Prognostic Factor than mTOR in Gastric Cancer.
作者信息
Cao Guo-Dong, Xu Xing-Yu, Zhang Jia-Wei, Chen Bo, Xiong Mao-Ming
机构信息
Anhui Medical University, Hefei, Anhui, China.
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
出版信息
PLoS One. 2016 Dec 22;11(12):e0168085. doi: 10.1371/journal.pone.0168085. eCollection 2016.
AIMS
The mammalian target of rapamycin (mTOR) and phosphorylated mTOR (p-mTOR) occurring downstream in the PI3K/Akt/mTOR pathway, are regarded as potential prognostic markers for gastric cancer (GC). However, the prognostic value of mTOR/p-mTOR expression remains controversial. In this study, we determined the expression of mTOR, p-mTOR, p70S6k, and p-p70S6K in GC, and investigated the correlation between their overexpression, clinicopathological parameters, and overall survival (OS).
METHODS
The expression of mTOR, p-mTOR, p70S6k, and p-p70S6K was examined in 120 GC patients by immunohistochemistry (IHC). The association of protein expression with clinicopathological features and OS was explored. The p-mTOR expression was detected in normal, adjacent, and GC tissues using Western blot. Eligible studies retrieved from PubMed, Ovid, Web of Science and Cochrane databases, were reviewed in this meta-analysis.
RESULTS
IHC showed that the rates of expression of the signal transduction molecules mTOR, p-mTOR, p70S6k and p-p70S6K in GC were 60.8%, 54.2%, 53.3% and 53.3%, respectively. Overexpression of mTOR and p70S6K showed no significant association with clinical variables. Expression of p-mTOR was significantly associated with differentiation (P < 0.01), depth of invasion (P < 0.01), lymph node metastasis (P = 0.04) and TNM stage (P = 0.02). Expression of p-p70S6K was associated with differentiation (P = 0.006), depth of invasion (P < 0.001), and TNM stage (P = 0.02). In survival analysis, differentiation, depth of invasion, lymph node metastasis and TNM stage were not related to OS (all P > 0.05). Furthermore, p-mTOR and p-p70S6K expression, but not mTOR and p70S6K, were tightly associated with OS of GC patients (P = 0.006 and P < 0.001, respectively). In Western blot, p-mTOR was significantly higher in GC tissues than in normal and adjacent tissues. In the present meta-analysis, mTOR overexpression showed no relationship with any clinicopathological variables. However, p-mTOR was correlated with depth of invasion, and TNM stage (all P < 0.05), and its overexpression was associated with a shorter survival time (P < 0.001).
CONCLUSION
The results suggest that p-mTOR is a more valuable prognostic factor than mTOR in GC.
目的
雷帕霉素哺乳动物靶点（mTOR）及磷酸化mTOR（p - mTOR）在PI3K/Akt/mTOR通路下游发挥作用，被视为胃癌（GC）潜在的预后标志物。然而，mTOR/p - mTOR表达的预后价值仍存在争议。在本研究中，我们测定了GC中mTOR、p - mTOR、p70S6k和p - p70S6K的表达，并研究了它们的过表达与临床病理参数及总生存期（OS）之间的相关性。
方法
采用免疫组织化学（IHC）法检测120例GC患者中mTOR、p - mTOR、p70S6k和p - p70S6K的表达。探讨蛋白表达与临床病理特征及OS的相关性。使用蛋白质印迹法检测正常组织、癌旁组织和GC组织中的p - mTOR表达。从PubMed、Ovid、Web of Science和Cochrane数据库检索的合格研究纳入本荟萃分析进行综述。
结果
免疫组化显示，GC中信号转导分子mTOR、p - mTOR、p70S6k和p - p70S6K的表达率分别为60.8%、54.2%、53.3%和53.3%。mTOR和p70S6K的过表达与临床变量无显著相关性。p - mTOR的表达与分化程度（P < 0.01）、浸润深度（P < 0.01）、淋巴结转移（P = 0.04）及TNM分期（P = 0.02）显著相关。p - p70S6K的表达与分化程度（P = 0.006）、浸润深度（P < 0.001）及TNM分期（P = 0.02）相关。生存分析中，分化程度、浸润深度、淋巴结转移和TNM分期与OS均无相关性（所有P > 0.05）。此外，p - mTOR和p - p70S6K的表达与GC患者的OS密切相关（分别为P = 0.006和P < 0.001），而mTOR和p70S6K则不然。蛋白质印迹法显示，GC组织中的p - mTOR显著高于正常组织和癌旁组织。在本荟萃分析中，mTOR过表达与任何临床病理变量均无关联。然而，p - mTOR与浸润深度和TNM分期相关（所有P < 0.05），其过表达与较短的生存时间相关（P < 0.001）。
结论
结果表明，在GC中p - mTOR是比mTOR更有价值的预后因素。
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