INPP4B、Akt、pAkt在食管鳞癌中的表达及其与预后的关系

发布时间：2018-05-06 23:07

本文选题：食管癌 + II型多磷酸肌醇4-磷酸酶　；参考：《山西医科大学》2017年硕士论文

【摘要】：食管癌是人类常见的恶性肿瘤之一,在我国,食管癌的发病率与死亡率均居国内肿瘤原因致死的前列。研究发现,在多种肿瘤细胞都发生了信号传导通路的异常改变。其中,PI3K-Akt-mtor传导通路在细胞的生长、繁殖中起着重要作用,与人类多种肿瘤的发生发展密切相关。在食管癌中,PI3K/Akt通路异常激活,PI3K及Akt蛋白存在着异常高表达,其在肿瘤的血管形成及转移中起着重要作用。近年来,多种研究发现,与抑癌基因PTEN作用机制相似,INPP4B通过抑制PI3K/Akt通路,在多种肿瘤中起着抑癌基因的作用。目前国内外关于INPP4B在食管癌中的研究较少,因此,我们决定对INPP4B及与之相关的Akt及pAkt在食管癌中作用进行研究。本研究应用实时定量PCR(qRT-PCR)检测INPP4BmRNA在食管鳞癌组织及其相对应的癌旁组织中的表达,运用免疫组化检测INPP4B、Akt、pAkt蛋白在食管鳞癌中的表达,并探讨这三者在食管鳞癌中的作用及其与食管癌患者预后的关系。目的:探讨II型多磷酸肌醇4-磷酸酶(inositol polyphosphate-4-phosphatase type II,INPP4B)及Akt和pAkt在食管鳞癌组织中的表达及其与预后的关系。方法:采用实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)检测32例食管癌患者的癌组织及相应的癌旁组织中(距癌组织大于5cm)中INPP4BmRNA的表达情况,并分析其与食管癌临床病理特征之间的关系。采用免疫组织化学SP法检测70例食管癌组织及20例正常食管上皮组织中INPP4B、Akt和pAkt蛋白的表达情况,并分析其对食管癌预后的影响及其与食管癌临床病理特征的关系。结果:应用荧光定量PCR技术对32对食管鳞癌及癌旁组织中INPP4B的表达情况进行验证。食管鳞癌组织中INPP4B表达上调的例数为21(65.5%),相对于癌旁组织,INPP4B在食管鳞癌组织中有统计学意义上的高表达(p0.05)。在70例食管癌组织中及20例正常食管上皮组织中,INPP4B蛋白的表达率显著高于正常食管组织(67.1%vs40%,P0.05),Akt及p AKT蛋白的表达率显著高于正常食管组织(72.8%vs 25%;82.8%vs 15%,均P0.05).INPP4B蛋白的表达水平与食管癌患者的年龄、性别及临床病理特征无明显相关(均P0.05);Akt蛋白的表达水平与肿瘤直径、分化程度、淋巴结转移及TNM均有关(均P0.05).p Akt蛋白的表达水平与淋巴结转移有关,与年龄、性别及临床病理特征无关。INPP4B与Akt蛋白表达呈正相关(r=0.531,P=0.000).与p Akt的表达呈正相关(r=0.327,P=0.000).INPP4B蛋白高表达患者术后生存率明显低于低表达患者(P=0.000),Akt蛋白高表达患者术后生存率明显低于低表达患者(P=0.000).p Akt蛋白高表达患者术后生存率明显低于低表达患者(P=0.000).结论:INPP4B mRNA及蛋白均在食管癌组织中表达上调,与食管癌的分化程度、淋巴结转移及TNM分期无关。Akt在食管癌中的表达上调,并与食管癌患者的临床病理因素密切相关。pAkt与食管癌淋巴结转移有关。INPP4B可能在食管癌中起着癌基因的作用,其研究可能为食管癌的治疗提供新的方向,INPP4B对评估患者的预后有一定预示作用。
[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.

【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.1

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