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

【摘要】：研究背景：胃癌是源于胃黏膜上皮細(xì)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(jì)欠發(fā)達(dá)國(guó)家和地區(qū),中國(guó)及其他東亞國(guó)家高發(fā)。在臨床上,常用外科手術(shù)切除加區(qū)域淋巴結(jié)清掃及術(shù)后放化療支持,盡管早期胃癌的治療已經(jīng)取得了重大進(jìn)步,但晚期胃癌的長(zhǎng)期生存率仍然很低。研究表明,腫瘤的侵襲、轉(zhuǎn)移導(dǎo)致了大部分胃癌患者的死亡并在胃癌的不良預(yù)后中扮演了關(guān)鍵角色。胃癌的侵襲、轉(zhuǎn)移是一個(gè)多基因調(diào)控、多因子參與、多步驟進(jìn)行的復(fù)雜的生物學(xué)過程,一般認(rèn)為癌細(xì)胞具有的運(yùn)動(dòng)和侵襲能力是產(chǎn)生轉(zhuǎn)移的重要條件。但對(duì)于晚期胃癌,其侵襲和轉(zhuǎn)移潛在的分子機(jī)制尚不明確。因而尋找可靠的腫瘤預(yù)后的標(biāo)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(diǎn),改善腫瘤的預(yù)后,是近年來研究的熱點(diǎn),也是腫瘤研究中的一個(gè)重點(diǎn)和難點(diǎn)。因此,迫切的需要鑒別胃癌進(jìn)展期的重要分子,研發(fā)新的藥物作用靶點(diǎn),為腫瘤的治療和患者的預(yù)后提供有價(jià)值的幫助。T淋巴瘤轉(zhuǎn)移誘導(dǎo)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(dǎo)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(hào)途徑,改變腫瘤細(xì)胞的形態(tài)和功能,調(diào)節(jié)并誘導(dǎo)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(xì)胞中異常表達(dá),如鼻咽癌、乳腺癌、結(jié)直腸癌、視網(wǎng)膜母細(xì)胞瘤、原發(fā)性肝癌、Ras誘導(dǎo)的皮膚腫瘤等,并與這些腫瘤的早期診斷和不良預(yù)后關(guān)系密切,但尚未見其異常表達(dá)與胃腺癌及其預(yù)后之間關(guān)系的研究。目的：明確Tiaml蛋白在胃腺癌組織及細(xì)胞中的表達(dá)和定位,并結(jié)合臨床病理資料,分析Tiaml過表達(dá)與胃腺癌轉(zhuǎn)移、侵襲和不良預(yù)后的相關(guān)性,為Tiaml作為胃腺癌轉(zhuǎn)移、侵襲和不良預(yù)后的分子靶點(diǎn)提供理論和實(shí)驗(yàn)依據(jù)。方法：采用免疫組化EnVision法檢測(cè)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(dá)及其與胃腺癌臨床病理特征之間的關(guān)系,采用免疫熒光染色法檢測(cè)Tiaml在胃腺癌細(xì)胞中的定位情況,分析Tiaml在胃癌中過表達(dá)以及與胃腺癌患者預(yù)后的相關(guān)性；通過生存期分析驗(yàn)證Tiaml在胃癌患者預(yù)后評(píng)估中的標(biāo)志物作用。結(jié)果：(1)Tiaml蛋白在胃腺癌組織和細(xì)胞中過表達(dá),主要表達(dá)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(qiáng)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(dá)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(rùn)密切相關(guān)(P0.05),與患者性別、年齡及腫塊大小等均無關(guān)。在中、低分化胃腺癌中,Tiaml蛋白強(qiáng)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(dá)亦顯著增強(qiáng)；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(jìn)展期胃腺癌中的表達(dá)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(dá)73.3%(44/60),在發(fā)生漿膜浸潤(rùn)的胃腺癌中,Tiaml陽性率高達(dá)73.8%(45/61)(3)生存期分析顯示,Tiaml高表達(dá)的胃癌患者的生存期低于Tiaml低表達(dá)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(dá)的胃癌患者的生存期低于Tiaml低表達(dá)患者；在發(fā)生漿膜浸潤(rùn)的胃腺癌患者中,Tiaml高表達(dá)的胃癌患者的生存期低于Tiaml低表達(dá)患者。結(jié)論：(1)Tiaml在胃腺癌組織和細(xì)胞中過表達(dá),且主要定位于細(xì)胞漿中；(2) Tiaml過表達(dá)與胃腺癌的轉(zhuǎn)移、侵襲和不良預(yù)后密切相關(guān)； (3)Tiaml蛋白過表達(dá)有望成為胃腺癌預(yù)后不良的有效檢測(cè)指標(biāo)及分子治療靶點(diǎn)。
[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(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.2

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