mTOR和p-mTOR在胃癌組織中的表達(dá)和臨床意義
發(fā)布時(shí)間:2018-06-22 00:07
本文選題:胃癌 + 雷帕霉素靶蛋白。 參考:《安徽醫(yī)科大學(xué)》2017年碩士論文
【摘要】:目的:PI3K/Akt/mTOR通路下游信號分子哺乳動(dòng)物雷帕霉素靶蛋白(mTOR)和磷酸化哺乳動(dòng)物雷帕霉素靶蛋白(p-mTOR)在胃癌組織中被認(rèn)為是潛在的預(yù)后指標(biāo)。但是mTOR和p-mTOR的預(yù)后價(jià)值仍存在爭議。此研究通過檢測胃癌組織中mTOR、p-mTOR、p70核糖體蛋白S6激酶(p70S6k)及磷酸化p70S6K(p-p70S6K)的表達(dá)情況,探討其表達(dá)情況和胃癌患者臨床病理參數(shù)和術(shù)后生存之間的關(guān)系。方法:通過免疫組化方法檢測120例胃癌患者胃癌組織中mTOR、p-mTOR、p70S6k及p-p70S6K的表達(dá)情況,分析其表達(dá)和胃癌患者臨床病理參數(shù)和術(shù)后生存之間的關(guān)系。通過同時(shí)應(yīng)用Western blot(WB)技術(shù)檢測正常、癌旁及胃癌組織中p-mTOR表達(dá)水平。從Pub Med、Ovid、Web of Science及Cochrane數(shù)據(jù)庫中篩選相關(guān)文獻(xiàn),完成薈萃分析。結(jié)果:免疫組化結(jié)果顯示信號轉(zhuǎn)導(dǎo)通路分子mTOR、p-mTOR、p70S6k及p-p70S6K在胃癌組織中的表達(dá)率分別為60.8%、54.2%、53.3%和53.3%。mTOR和p70S6K未顯示和臨床病理參數(shù)存在相關(guān)性。p-mTOR和胃癌組織分化程度(P0.01)、浸潤深度(P0.01)、淋巴結(jié)轉(zhuǎn)移(P=0.04)以及TNM分期(P=0.02)顯著相關(guān)。同時(shí)p-p70S6K和分化程度(P=0.006)、浸潤深度(P0.001)及TNM分期(P=0.02)存在明顯關(guān)聯(lián)。生存分析顯示分化程度、浸潤深度、淋巴結(jié)轉(zhuǎn)移、TNM分期和患者術(shù)后生存情況無明顯關(guān)系(所有P值0.05)。p-mTOR和p-p70S6K和胃癌患者術(shù)后總體生存具有密切關(guān)系(P=0.006及P0.001)。WB結(jié)果顯示p-mTOR表達(dá)水平于胃癌組織中較正常和癌旁組織明顯升高。薈萃分析結(jié)果表明mTOR和臨床病理參數(shù)以及術(shù)后總體生存無關(guān),p-mTOR和浸潤深度(P0.05)、TNM分期(P0.05)顯著相關(guān),其過表達(dá)往往預(yù)示著更短的術(shù)后生存時(shí)間(P0.001)。結(jié)論:較mTOR而言,p-mTOR可作為胃癌組織中更有價(jià)值的預(yù)后指標(biāo)。
[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.
【學(xué)位授予單位】:安徽醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R735.2
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本文編號:2050640
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