NOTUM基因在胃腸道腫瘤中的表達(dá)及臨床意義
發(fā)布時(shí)間:2018-06-01 07:44
本文選題:胃癌 + 結(jié)腸癌; 參考:《中國(guó)人民解放軍醫(yī)學(xué)院》2017年碩士論文
【摘要】:背景胃腸道腫瘤嚴(yán)重危害著人類的健康,最新的ca雜志表明,在中國(guó),胃癌在所有腫瘤中發(fā)病率和死亡率都高居第二位。雖然隨著放療化療及免疫治療的不斷發(fā)展,胃癌的生存期有所延長(zhǎng)。但是由于發(fā)現(xiàn)不及時(shí),腫瘤大部分都在中晚期,使得胃癌的總體生存率不足30%。故早期發(fā)現(xiàn)胃癌及發(fā)現(xiàn)有效腫瘤標(biāo)記物從而早期診斷早期防治是提高生存率的有效途徑。NOTUM基因是一種新興發(fā)現(xiàn)的基因,在斑馬魚中已經(jīng)得到證實(shí)可以通過去磷酸化有效抑制wnt信號(hào)通路,而在人類肝癌中發(fā)現(xiàn)高表達(dá),與wnt信號(hào)通路存在負(fù)反饋調(diào)節(jié)的作用。而在胃腸道腫瘤的研究尚未清晰,本研究探索NOTUM基因在結(jié)腸癌及胃癌中的表達(dá)及臨床意義。目的檢測(cè)NOTUM基因在胃癌組織中的表達(dá)情況,探討其與胃癌患者的臨床病理關(guān)系。研究wnt信號(hào)通路與NOTUM基因的相互影響關(guān)系,檢測(cè)NOTUM基因在結(jié)腸癌組織中的表達(dá)情況,探討其與結(jié)腸癌患者的臨床病理關(guān)系。進(jìn)一步探索NOTUM基因在消化道腫瘤中作用。方法收集胃癌及結(jié)腸癌組織標(biāo)本,分別通過免疫組化方法檢測(cè)組織中的NOTUM基因表達(dá)情況,分析NOTUM基因的表達(dá)與患者的臨床病理及預(yù)后的關(guān)系,使用免疫印跡方法檢測(cè)NOTUM蛋白與β-catenin蛋白的表達(dá)量,使用SPSS進(jìn)行相關(guān)性分析確定NOTUM蛋白與β-catenin蛋白之間的關(guān)系。應(yīng)用Kaplan-Meier方法比較NOTUM陽(yáng)性表達(dá)胃癌患者與陰性表達(dá)胃癌患者在術(shù)后生存時(shí)間的差異。分別采用Log-rank檢驗(yàn)和Cox回歸模型對(duì)可能影響預(yù)后的臨床病理特征進(jìn)行單因素和多因素分析。結(jié)果(1)胃癌組織中NOTUM基因的表達(dá)顯著增加,其表達(dá)與淋巴結(jié)轉(zhuǎn)移及TNM分期及預(yù)后生存相關(guān)(p0.05),與患者的年齡、性別、腫瘤發(fā)生部位、腫瘤大小及腫瘤病理類型無(wú)關(guān)。胃癌組織中NOTUM基因和β-catenin蛋白的表達(dá)呈正相關(guān)。在NOTUM基因表達(dá)陽(yáng)性的胃癌患者的生存時(shí)間明顯縮短。NOTUM基因表達(dá)可以作為影響胃癌患者生存的獨(dú)立危險(xiǎn)因素(2)結(jié)腸癌組織中NOTUM基因的表達(dá)顯著增加,其表達(dá)與淋巴結(jié)轉(zhuǎn)移及TNM分期及預(yù)后生存相關(guān)(p0.05),與患者的年齡、性別、腫瘤大小及腫瘤病理類型無(wú)關(guān)。在NOTUM基因表達(dá)陽(yáng)性的結(jié)腸癌患者的生存時(shí)間明顯縮短。NOTUM基因表達(dá)可以作為影響結(jié)腸癌患者生存的獨(dú)立危險(xiǎn)因素結(jié)論胃癌及結(jié)腸癌中NOTUM基因在呈高表達(dá),可作為判斷胃癌及結(jié)腸癌患者疾病進(jìn)展及預(yù)后的生物學(xué)標(biāo)記物。
[Abstract]:Background Gastrointestinal cancer is a serious hazard to human health. The latest CA journal shows that gastric cancer is the second leading cause of morbidity and mortality among all tumors in China. Although with the continuous development of radiotherapy, chemotherapy and immunotherapy, gastric cancer survival has been prolonged. However, due to the late detection, most of the tumors are in the late stage, resulting in the overall survival rate of gastric cancer is less than 30. Therefore, the early detection of gastric cancer and the discovery of effective tumor markers for early diagnosis and prevention are effective ways to improve survival rate. NOTUM gene is a newly discovered gene. It has been proved that the wnt signaling pathway can be effectively inhibited by dephosphorylation in zebrafish, while high expression has been found in human hepatocellular carcinoma, and there is a negative feedback regulation with wnt signal pathway. The expression and clinical significance of NOTUM gene in colon cancer and gastric cancer were not clear. Objective to investigate the expression of NOTUM gene in gastric cancer and its clinicopathological relationship. To study the relationship between wnt signaling pathway and NOTUM gene, to detect the expression of NOTUM gene in colon cancer tissues, and to explore the clinicopathological relationship between NOTUM and colon cancer patients. To further explore the role of NOTUM gene in digestive tract tumors. Methods the expression of NOTUM gene was detected by immunohistochemical method in gastric and colon cancer tissues, and the relationship between the expression of NOTUM gene and clinicopathology and prognosis was analyzed. The expression of NOTUM protein and 尾 -catenin protein was detected by Western blot, and the relationship between NOTUM protein and 尾 -catenin protein was determined by SPSS correlation analysis. Kaplan-Meier method was used to compare the survival time of NOTUM positive expression gastric cancer patients and negative expression gastric cancer patients. Log-rank test and Cox regression model were used to analyze the clinicopathological features which may affect the prognosis. Results 1) the expression of NOTUM gene was significantly increased in gastric cancer tissues. The expression of NOTUM gene was correlated with lymph node metastasis, TNM stage and prognosis (P 0.05), but not with age, sex, tumor location, tumor size and tumor pathological type. There was a positive correlation between the expression of NOTUM gene and 尾-catenin protein in gastric carcinoma. The survival time of gastric cancer patients with positive NOTUM gene expression was significantly shortened. NOTUM gene expression could be used as an independent risk factor for the survival of gastric cancer patients. Its expression was correlated with lymph node metastasis, TNM stage and prognosis, but not with age, sex, tumor size and tumor pathological type. The survival time of colon cancer patients with positive NOTUM gene expression was significantly shortened. NOTUM gene expression may be an independent risk factor for the survival of colon cancer patients. Conclusion the expression of NOTUM gene is high in gastric cancer and colon cancer. It can be used as a biological marker to judge the progression and prognosis of gastric and colon cancer patients.
【學(xué)位授予單位】:中國(guó)人民解放軍醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R735
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 訾永宏;姬樂;陳紅梅;李艷東;;Arl4c在結(jié)腸癌中的表達(dá)及其臨床意義[J];山西醫(yī)科大學(xué)學(xué)報(bào);2017年01期
2 張明基;應(yīng)敏剛;;WNT信號(hào)傳導(dǎo)通路與胃癌[J];中國(guó)腫瘤;2007年11期
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