mTOR和p-mTOR在胃癌组织中的表达和临床意义

发布时间：2018-06-22 00:07

本文选题：胃癌 + 雷帕霉素靶蛋白　；参考：《安徽医科大学》2017年硕士论文

【摘要】：目的:PI3K/Akt/mTOR通路下游信号分子哺乳动物雷帕霉素靶蛋白(mTOR)和磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)在胃癌组织中被认为是潜在的预后指标。但是mTOR和p-mTOR的预后价值仍存在争议。此研究通过检测胃癌组织中mTOR、p-mTOR、p70核糖体蛋白S6激酶(p70S6k)及磷酸化p70S6K(p-p70S6K)的表达情况,探讨其表达情况和胃癌患者临床病理参数和术后生存之间的关系。方法:通过免疫组化方法检测120例胃癌患者胃癌组织中mTOR、p-mTOR、p70S6k及p-p70S6K的表达情况,分析其表达和胃癌患者临床病理参数和术后生存之间的关系。通过同时应用Western blot(WB)技术检测正常、癌旁及胃癌组织中p-mTOR表达水平。从Pub Med、Ovid、Web of Science及Cochrane数据库中筛选相关文献,完成荟萃分析。结果:免疫组化结果显示信号转导通路分子mTOR、p-mTOR、p70S6k及p-p70S6K在胃癌组织中的表达率分别为60.8%、54.2%、53.3%和53.3%。mTOR和p70S6K未显示和临床病理参数存在相关性。p-mTOR和胃癌组织分化程度(P0.01)、浸润深度(P0.01)、淋巴结转移(P=0.04)以及TNM分期(P=0.02)显著相关。同时p-p70S6K和分化程度(P=0.006)、浸润深度(P0.001)及TNM分期(P=0.02)存在明显关联。生存分析显示分化程度、浸润深度、淋巴结转移、TNM分期和患者术后生存情况无明显关系(所有P值0.05)。p-mTOR和p-p70S6K和胃癌患者术后总体生存具有密切关系(P=0.006及P0.001)。WB结果显示p-mTOR表达水平于胃癌组织中较正常和癌旁组织明显升高。荟萃分析结果表明mTOR和临床病理参数以及术后总体生存无关,p-mTOR和浸润深度(P0.05)、TNM分期(P0.05)显著相关,其过表达往往预示着更短的术后生存时间(P0.001)。结论:较mTOR而言,p-mTOR可作为胃癌组织中更有价值的预后指标。
[Abstract]:Objective the downstream signaling molecules of the PI3K / Akt / mTOR pathway, mammalian rapamycin target protein (mTOR) and phosphorylated mammalian rapamycin target protein (p-mTOR), are considered as potential prognostic markers in gastric cancer. However, the prognostic value of mTOR and p-mTOR remains controversial. In this study, the expression of mTORP-mTORp70 ribosomal protein S6 kinase (p70S6k) and phosphorylated p70S6K (p-p70S6K) in gastric cancer tissues was detected, and the relationship between the expression of p70 S6K and clinicopathologic parameters and postoperative survival of gastric cancer patients was investigated. Methods: the expression of mTOR-p-mTORp70S6k and p-p70S6K in 120 patients with gastric cancer was detected by immunohistochemical method, and the relationship between the expression and clinicopathological parameters and postoperative survival was analyzed. The expression of p-mTOR in normal, paracancerous and gastric cancer tissues was detected by Western blot (WB). The relevant literatures were screened from the Pub MedOvidof Science and Cochrane database to complete the meta-analysis. Results: the expression rates of signal transduction pathway molecules mTORP p-mTORp70S6k and p-p70S6K in gastric cancer tissues were 60.8% and 54.2%, 53.3% and 53.3%, respectively. The expression rates of p-mTOR and p70S6K were not correlated with the clinicopathological parameters (P0.01), and the depth of invasion. (P 0.01), lymph node metastasis (P0. 04) and TNM staging (P0. 02) were significantly correlated. There was a significant correlation between p-p70S6K and differentiation (P0. 006), depth of infiltration (P0.001) and TNM staging (P0. 02). Survival analysis showed degree of differentiation, depth of infiltration, There was no significant relationship between TNM stage of lymph node metastasis and survival after operation (all P 0.05). P-mTOR and p-p70S6K were closely related to the overall survival of patients with gastric cancer (P0. 006 and P0. 001). WB results showed that the expression level of p-mTOR was higher than that of normal gastric cancer tissues and cancer. The side tissue increased obviously. The results of meta-analysis showed that mTOR had no correlation with clinicopathologic parameters and overall survival after operation (P0.05) and infiltration depth (P0.05) and TNM stage (P0.05). The overexpression of mTOR often predicted a shorter survival time (P0.001). Conclusion: p-mTOR may be a more valuable prognostic marker in gastric cancer than mTOR.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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