本文選題：胃腺癌 + T淋巴瘤轉(zhuǎn)移誘導因子��； 參考：《延邊大學》2016年碩士論文

【摘要】：研究背景：胃癌是源于胃黏膜上皮細胞的惡性腫瘤,主要為胃腺癌。2008年全球新診斷出胃癌近100萬例,病死人數(shù)74萬,是全世界發(fā)病率第四、致死率第二的癌癥,是臨床上常見的惡性腫瘤。雖然胃癌全球總發(fā)病率有所下降,但有近三分之二的胃癌病例集中于經(jīng)濟欠發(fā)達國家和地區(qū),中國及其他東亞國家高發(fā)。在臨床上,常用外科手術切除加區(qū)域淋巴結(jié)清掃及術后放化療支持,盡管早期胃癌的治療已經(jīng)取得了重大進步,但晚期胃癌的長期生存率仍然很低。研究表明,腫瘤的侵襲、轉(zhuǎn)移導致了大部分胃癌患者的死亡并在胃癌的不良預后中扮演了關鍵角色。胃癌的侵襲、轉(zhuǎn)移是一個多基因調(diào)控、多因子參與、多步驟進行的復雜的生物學過程,一般認為癌細胞具有的運動和侵襲能力是產(chǎn)生轉(zhuǎn)移的重要條件。但對于晚期胃癌,其侵襲和轉(zhuǎn)移潛在的分子機制尚不明確。因而尋找可靠的腫瘤預后的標志性因子,以及能夠有效抑制腫瘤轉(zhuǎn)移和侵襲的分子靶點,改善腫瘤的預后,是近年來研究的熱點,也是腫瘤研究中的一個重點和難點。因此,迫切的需要鑒別胃癌進展期的重要分子,研發(fā)新的藥物作用靶點,為腫瘤的治療和患者的預后提供有價值的幫助。T淋巴瘤轉(zhuǎn)移誘導因子(T-cell lymphoma invasion and metastasis-inducing factor, Tiaml)是Habets等于1994年從鼠的T淋巴瘤中分離出來的一種腫瘤轉(zhuǎn)移誘導基因,其產(chǎn)物Tiaml蛋白作為一種鳥苷酸轉(zhuǎn)換因子,特異性激活Rac-1,并通過Tiaml-Rac信號途徑,改變腫瘤細胞的形態(tài)和功能,調(diào)節(jié)并誘導腫瘤的侵襲和轉(zhuǎn)移。近年來的研究發(fā)現(xiàn),Tiaml蛋白在多種腫瘤組織和細胞中異常表達,如鼻咽癌、乳腺癌、結(jié)直腸癌、視網(wǎng)膜母細胞瘤、原發(fā)性肝癌、Ras誘導的皮膚腫瘤等,并與這些腫瘤的早期診斷和不良預后關系密切,但尚未見其異常表達與胃腺癌及其預后之間關系的研究。目的：明確Tiaml蛋白在胃腺癌組織及細胞中的表達和定位,并結(jié)合臨床病理資料,分析Tiaml過表達與胃腺癌轉(zhuǎn)移、侵襲和不良預后的相關性,為Tiaml作為胃腺癌轉(zhuǎn)移、侵襲和不良預后的分子靶點提供理論和實驗依據(jù)。方法：采用免疫組化EnVision法檢測Tiaml蛋白在102例胃腺癌組織、21例胃異型增生組織和33例癌旁正常組織中的表達及其與胃腺癌臨床病理特征之間的關系,采用免疫熒光染色法檢測Tiaml在胃腺癌細胞中的定位情況,分析Tiaml在胃癌中過表達以及與胃腺癌患者預后的相關性；通過生存期分析驗證Tiaml在胃癌患者預后評估中的標志物作用。結(jié)果：(1)Tiaml蛋白在胃腺癌組織和細胞中過表達,主要表達在胞漿中,并有核周聚集現(xiàn)象; (2)胃腺癌組織中Tiaml陽性率為85.3%(87/102),強陽性率為61.8%(63/102),均明顯高于胃異型組織和癌旁正常組織(P0.01)。Tiaml蛋白表達水平與胃腺癌分化程度、臨床分期、淋巴結(jié)轉(zhuǎn)移及漿膜浸潤密切相關(P0.05),與患者性別、年齡及腫塊大小等均無關。在中、低分化胃腺癌中,Tiaml蛋白強陽性率明顯高于高分化的胃腺癌病例(P0.01),表明隨著胃腺癌惡性程度的增加,Tiaml蛋白的表達亦顯著增強；在Ⅰ～Ⅱ期的胃腺癌中陽性率為51.1%(24/47),在Ⅲ～Ⅳ期的胃腺癌中陽性率為70.9%(39/55),表明Tiaml在進展期胃腺癌中的表達明顯高于早期胃腺癌；在發(fā)生淋巴結(jié)轉(zhuǎn)移的胃腺癌中,Tiaml陽性率高達73.3%(44/60),在發(fā)生漿膜浸潤的胃腺癌中,Tiaml陽性率高達73.8%(45/61)(3)生存期分析顯示,Tiaml高表達的胃癌患者的生存期低于Tiaml低表達患者；單因素分析顯示,在發(fā)生淋巴結(jié)轉(zhuǎn)移的胃腺癌患者中,Tiaml高表達的胃癌患者的生存期低于Tiaml低表達患者；在發(fā)生漿膜浸潤的胃腺癌患者中,Tiaml高表達的胃癌患者的生存期低于Tiaml低表達患者。結(jié)論：(1)Tiaml在胃腺癌組織和細胞中過表達,且主要定位于細胞漿中；(2) Tiaml過表達與胃腺癌的轉(zhuǎn)移、侵襲和不良預后密切相關； (3)Tiaml蛋白過表達有望成為胃腺癌預后不良的有效檢測指標及分子治療靶點。
[Abstract]:Background: gastric cancer is a malignant tumor originate from the epithelial cells of the gastric mucosa. It is mainly the new diagnosis of gastric cancer in the.2008 year of.2008. The death rate is 740 thousand, the incidence of the world is fourth, the mortality rate is second, and it is a common malignant tumor in the clinic. Although the total global incidence of gastric cancer has decreased, it has nearly 2/3 The cases of gastric cancer are concentrated in economically undeveloped countries and regions, in China and in other East Asian countries. In clinic, surgical excision, regional lymph node dissection and postoperative radiotherapy and chemotherapy support are commonly used. Although significant progress has been made in the treatment of early gastric cancer, the long-term survival rate of advanced gastric cancer is still low. Invasion and metastasis lead to the death of most patients with gastric cancer and play a key role in the bad prognosis of gastric cancer. The invasion and metastasis of gastric cancer is a multi gene regulation, multi factor participation and complex biological processes in many steps. It is generally believed that the transport and invasion ability of cancer cells is an important condition for the generation of metastasis. In advanced gastric cancer, the potential molecular mechanisms of invasion and metastasis are not clear. Therefore, it is a hot spot in recent years to find a reliable marker for tumor prognosis, as well as the molecular targets that can effectively inhibit tumor metastasis and invasion, and to improve the prognosis of tumor. Therefore, it is an urgent need. Identifying important molecules in the progression of gastric cancer, developing new drug targets, providing valuable help for.T lymphoma metastasis inducible factor (T-cell lymphoma invasion and metastasis-inducing factor, Tiaml) is a tumor metastasis isolated from T lymphoma of mice in 1994. The inducible gene, the Tiaml protein, as a kind of guanosine conversion factor, specifically activates Rac-1, and changes the morphology and function of tumor cells through the Tiaml-Rac signal pathway to regulate and induce tumor invasion and metastasis. Recent studies have found that Tiaml protein is abnormal expression in various tumor tissues and cells, such as nasopharyngeal carcinoma and mammary gland. Cancer, colorectal cancer, retinoblastoma, primary liver cancer, Ras induced skin tumor and so on, which are closely related to the early diagnosis and poor prognosis of these tumors, but the relationship between abnormal expression and gastric adenocarcinoma and its prognosis has not been seen. Objective: to clarify the expression and localization of Tiaml protein in gastric adenocarcinoma tissue and cells, and to determine the relationship between the expression and localization of gastric adenocarcinoma. The correlation between Tiaml overexpression and metastasis of gastric adenocarcinoma, invasion and poor prognosis was analyzed with clinical and pathological data. The theoretical and experimental basis was provided for Tiaml as a molecular target for metastasis, invasion and poor prognosis of gastric adenocarcinoma. Methods: immunohistochemistry EnVision method was used to detect Tiaml protein in 102 gastric adenocarcinoma tissues, 21 cases of gastric dysplasia and 3 The relationship between the expression of normal paracancerous tissues and the clinicopathological features of gastric adenocarcinoma was observed in 3 cases. The location of Tiaml in gastric adenocarcinoma cells was detected by immunofluorescence staining, and the correlation between the overexpression of Tiaml in gastric cancer and the prognosis of gastric adenocarcinoma patients was analyzed. The prognostic evaluation of Tiaml in gastric cancer patients was verified by the survival time analysis. Results: (1) the expression of Tiaml protein in gastric adenocarcinoma tissue and cells, mainly expressed in the cytoplasm, and the phenomenon of perinuclear aggregation; (2) the positive rate of Tiaml in gastric adenocarcinoma was 85.3% (87/102), and the strong positive rate was 61.8% (63/102), which was significantly higher than the expression level of.Tiaml protein in the gastric anypical tissues and adjacent normal tissues (P0.01). The degree of differentiation, clinical stage, lymph node metastasis and serous infiltration were closely related to gastric adenocarcinoma (P0.05), not related to sex, age and size of the tumor. In low differentiated gastric adenocarcinoma, the strong positive rate of Tiaml protein was significantly higher than that of highly differentiated gastric adenocarcinoma (P0.01), indicating that with the increase of malignancy of gastric adenocarcinoma, the expression of Tiaml protein The positive rate of gastric adenocarcinoma in stage I to stage II was 51.1% (24/47), and the positive rate in gastric adenocarcinoma in stage III to IV was 70.9% (39/55), indicating that the expression of Tiaml in advanced gastric adenocarcinoma was significantly higher than that of early gastric adenocarcinoma, and the positive rate of Tiaml was up to 73.3% (44/60) in the gastric adenocarcinoma which had lymph node metastasis, and was in serous infiltration. In gastric adenocarcinoma, the Tiaml positive rate was up to 73.8% (45/61) (3) (3) survival analysis showed that the survival period of Tiaml high expression of gastric cancer patients was lower than that of Tiaml low expression patients; one factor analysis showed that in the patients with gastric adenocarcinoma with lymph node metastasis, the survival time of the patients with Tiaml high expression of gastric cancer was lower than that of the low expression of Tiaml; in the occurrence of serous dipping In the patients with gastric adenocarcinoma, the survival period of Tiaml high expression of gastric cancer patients was lower than that of Tiaml low expression patients. Conclusion: (1) Tiaml is overexpressed in gastric adenocarcinoma tissue and cells, and mainly located in the cytoplasm; (2) Tiaml overexpression is closely related to metastasis of gastric adenocarcinoma, invasion and bad preconditioning; (3) the overexpression of Tiaml protein is expected to become the stomach. Effective detection targets and molecular therapeutic targets for poor prognosis of adenocarcinoma.

【學位授予單位】：延邊大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R735.2

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