本文選題：食管癌 + II型多磷酸肌醇4-磷酸酶　； 參考：《山西醫(yī)科大學》2017年碩士論文

【摘要】：食管癌是人類常見的惡性腫瘤之一,在我國,食管癌的發(fā)病率與死亡率均居國內(nèi)腫瘤原因致死的前列。研究發(fā)現(xiàn),在多種腫瘤細胞都發(fā)生了信號傳導通路的異常改變。其中,PI3K-Akt-mtor傳導通路在細胞的生長、繁殖中起著重要作用,與人類多種腫瘤的發(fā)生發(fā)展密切相關。在食管癌中,PI3K/Akt通路異常激活,PI3K及Akt蛋白存在著異常高表達,其在腫瘤的血管形成及轉(zhuǎn)移中起著重要作用。近年來,多種研究發(fā)現(xiàn),與抑癌基因PTEN作用機制相似,INPP4B通過抑制PI3K/Akt通路,在多種腫瘤中起著抑癌基因的作用。目前國內(nèi)外關于INPP4B在食管癌中的研究較少,因此,我們決定對INPP4B及與之相關的Akt及pAkt在食管癌中作用進行研究。本研究應用實時定量PCR(qRT-PCR)檢測INPP4BmRNA在食管鱗癌組織及其相對應的癌旁組織中的表達,運用免疫組化檢測INPP4B、Akt、pAkt蛋白在食管鱗癌中的表達,并探討這三者在食管鱗癌中的作用及其與食管癌患者預后的關系。目的:探討II型多磷酸肌醇4-磷酸酶(inositol polyphosphate-4-phosphatase type II,INPP4B)及Akt和pAkt在食管鱗癌組織中的表達及其與預后的關系。方法:采用實時熒光定量PCR(quantitative real-time PCR,qRT-PCR)檢測32例食管癌患者的癌組織及相應的癌旁組織中(距癌組織大于5cm)中INPP4BmRNA的表達情況,并分析其與食管癌臨床病理特征之間的關系。采用免疫組織化學SP法檢測70例食管癌組織及20例正常食管上皮組織中INPP4B、Akt和pAkt蛋白的表達情況,并分析其對食管癌預后的影響及其與食管癌臨床病理特征的關系。結(jié)果:應用熒光定量PCR技術對32對食管鱗癌及癌旁組織中INPP4B的表達情況進行驗證。食管鱗癌組織中INPP4B表達上調(diào)的例數(shù)為21(65.5%),相對于癌旁組織,INPP4B在食管鱗癌組織中有統(tǒng)計學意義上的高表達(p0.05)。在70例食管癌組織中及20例正常食管上皮組織中,INPP4B蛋白的表達率顯著高于正常食管組織(67.1%vs40%,P0.05),Akt及p AKT蛋白的表達率顯著高于正常食管組織(72.8%vs 25%;82.8%vs 15%,均P0.05).INPP4B蛋白的表達水平與食管癌患者的年齡、性別及臨床病理特征無明顯相關(均P0.05);Akt蛋白的表達水平與腫瘤直徑、分化程度、淋巴結(jié)轉(zhuǎn)移及TNM均有關(均P0.05).p Akt蛋白的表達水平與淋巴結(jié)轉(zhuǎn)移有關,與年齡、性別及臨床病理特征無關。INPP4B與Akt蛋白表達呈正相關(r=0.531,P=0.000).與p Akt的表達呈正相關(r=0.327,P=0.000).INPP4B蛋白高表達患者術后生存率明顯低于低表達患者(P=0.000),Akt蛋白高表達患者術后生存率明顯低于低表達患者(P=0.000).p Akt蛋白高表達患者術后生存率明顯低于低表達患者(P=0.000).結(jié)論:INPP4B mRNA及蛋白均在食管癌組織中表達上調(diào),與食管癌的分化程度、淋巴結(jié)轉(zhuǎn)移及TNM分期無關。Akt在食管癌中的表達上調(diào),并與食管癌患者的臨床病理因素密切相關。pAkt與食管癌淋巴結(jié)轉(zhuǎn)移有關。INPP4B可能在食管癌中起著癌基因的作用,其研究可能為食管癌的治療提供新的方向,INPP4B對評估患者的預后有一定預示作用。
[Abstract]:Esophageal cancer is one of the most common malignant tumors in human beings. In China, the incidence and mortality of esophageal cancer are in the forefront of the death of cancer causes in China. It is found that the abnormal changes in the signal transduction pathways have occurred in various tumor cells. Among them, the PI3K-Akt-mtor conduction pathway plays an important role in the growth of fine cells, and is an important role in the reproduction. The development of various tumors is closely related. In esophageal cancer, PI3K/Akt pathway is abnormal activation, PI3K and Akt proteins have abnormal high expression, which play an important role in the angiogenesis and metastasis of tumor. In recent years, many studies have found that INPP4B is similar to the mechanism of the action of tumor suppressor gene PTEN. By inhibiting the PI3K/Akt pathway, INPP4B is in a variety of tumors. It plays a role in the tumor suppressor gene. At present, there are few studies on INPP4B in esophageal cancer. Therefore, we have decided to study the role of INPP4B and the associated Akt and pAkt in esophageal cancer. The present study used real-time quantitative PCR (qRT-PCR) to detect the expression of INPP4BmRNA in the tissues of squamous cell carcinoma of the esophagus and the corresponding para cancerous tissues. The expression of INPP4B, Akt, pAkt protein in esophageal squamous carcinoma was detected by immunohistochemistry and the role of these three in esophageal squamous cell carcinoma and its relationship with the prognosis of esophageal cancer patients. Objective: To explore the table of II type polyphosphate inositol 4- phosphatase (inositol polyphosphate-4-phosphatase type II, INPP4B) and Akt and pAkt in esophageal squamous cell carcinoma Method: the relationship between the expression of INPP4BmRNA in 32 cases of esophageal cancer and the corresponding para cancerous tissue greater than 5cm was detected by real-time PCR (quantitative real-time PCR, qRT-PCR), and the relationship between them and the clinicopathological features of esophageal cancer was analyzed. Immunohistochemical SP was used. The expression of INPP4B, Akt and pAkt protein in 70 cases of esophageal carcinoma and 20 cases of normal esophageal epithelium were detected by method. The relationship between the prognosis of esophageal cancer and the clinicopathological features of esophageal cancer were analyzed. Results: the expression of INPP4B in 32 pairs of esophageal squamous cell carcinoma and adjacent tissues was verified by fluorescence quantitative PCR. The number of up regulation of INPP4B expression in the squamous cell carcinoma was 21 (65.5%). Compared with the adjacent tissue, INPP4B had a statistically high expression in the esophageal squamous cell carcinoma (P0.05). In 70 cases of esophageal cancer and 20 normal esophageal epithelium, the expression rate of INPP4B protein was significantly higher than that of normal esophageal tissue (67.1%vs40%, P0.05), Akt and P AKT The expression rate of protein was significantly higher than that of normal esophageal tissue (72.8%vs 25%; 82.8%vs 15%, P0.05).INPP4B protein expression level had no significant correlation with age, sex and clinicopathological features of esophageal cancer patients (P0.05). The expression level of Akt protein was related to tumor diameter, differentiation, lymph node metastasis and TNM (P0.05).P Akt protein The expression level was associated with lymph node metastasis. The expression of.INPP4B was positively correlated with the expression of Akt protein (r=0.531, P=0.000) with age, sex and clinicopathological features. There was a positive correlation with the expression of P Akt (r=0.327, P=0.000). The survival rate of the patients with high expression of.INPP4B protein was significantly lower than that of the low expression patients (P=0.000), and the survival of the patients with high expression of Akt protein was the survival of the patients. The survival rate of patients with high expression of.P Akt protein (P=0.000) was significantly lower than that of low expression patients (P=0.000). Conclusion: the expression of INPP4B mRNA and protein are up regulated in esophageal cancer tissues, and the expression of.Akt in esophageal cancer is not up regulated in the degree of differentiation of esophageal cancer, lymph node metastasis and TNM stage, and with the patients with esophageal cancer. The clinical and pathological factors closely related to.PAkt and lymph node metastasis of esophageal cancer may play the role of.INPP4B in the cancer of the esophagus. The study may provide a new direction for the treatment of esophageal cancer, and INPP4B has a certain prognostic role in evaluating the prognosis of the patients.

【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.1

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