發(fā)布時間：2018-08-03 19:28

【摘要】：胃癌是一種嚴(yán)重威脅人們健康的多因素復(fù)雜疾病,在全世界的發(fā)病率僅次于肺癌、乳腺癌。雖然隨著科技進步,胃癌的手術(shù)治療已得到一定改善,但是由于該病的早期癥狀不明顯,不易引起人們的注意,造成人們在就診時已發(fā)展至晚期,使得該病的5年存活率只有20%-30%。為了提高胃癌的早期診斷與預(yù)防水平,尋找與胃癌發(fā)生相關(guān)的可靠分子標(biāo)志物就顯得尤為重要。而Wnt信號通路對于胃癌的發(fā)生起著非常重要的作用,該通路中一些抑制基因的的異常表達(dá)會使該通路活化,導(dǎo)致胃癌發(fā)生。因此本實驗主要通過對Wnt信號通路中一些抑制基因(DKK1、DKK2、DKK3、 SFRP2、SFRP5、SFRP4、AXIN2、APC)表達(dá)的研究以及其表達(dá)水平與病理參數(shù)的相關(guān)性分析,力爭探求胃癌診斷與預(yù)防的腫瘤分子標(biāo)志物,從而為胃癌的提早判斷及臨床預(yù)測提供一定參考。實驗中共收集40例符合要求的癌及癌旁組織,通過RT-PCR Taqman探針法檢測Wnt抑制基因的表達(dá),而后利用2-Act及2-△△ct公式對表達(dá)數(shù)據(jù)進行處理,最后將表達(dá)數(shù)據(jù)與臨床病理數(shù)據(jù)進行統(tǒng)計分析。本課題主要得出以下結(jié)論：a、2-△c值經(jīng)Mann-Whitney單尾非參數(shù)秩和檢驗后,發(fā)現(xiàn)DKK2(P0.0001)、SFRP2(P=0.049)、SFRP5(P=0.004)3個基因在胃癌發(fā)生中表達(dá)水平明顯降低,；DKK1、DKK3、、SFRP4、、AXIN2、APC5個基因在兩類組織中的相對表達(dá)沒有明顯差異,說明DKK2、SFRP2、SFRP5這3個基因的表達(dá)下調(diào),對胃癌發(fā)生有著十分重要的作用;b、2-△△ct經(jīng)非參數(shù)秩和檢驗結(jié)果顯示,在胃癌中DKK、SFRP2、SFRP5這3個基因相比該通路中的其他基因表達(dá)明顯下調(diào),說明這3個基因可能在該通路活化中起著更為重要的作用;c、將表達(dá)結(jié)果與病理數(shù)據(jù)用t檢驗分析發(fā)現(xiàn),這8個基因的差異表達(dá)都與年齡、性別和分化程度沒有關(guān)系；但是DKKK1、DKK2、DKK3、SFRP2、SFRP4、APC這6個基因的表達(dá)水平與患者的臨床分期顯著相關(guān)；所有抑制劑的異常表達(dá)都同患者的lymph node轉(zhuǎn)移在統(tǒng)計學(xué)上也具有顯著性。綜上所述,Wnt信號通路抑制基因的異常表達(dá)在胃癌的發(fā)生中起著重要作用,相關(guān)基因的表達(dá)下調(diào)與胃癌的發(fā)生及進展密切相關(guān),其有可能作為胃癌早期診斷的分子標(biāo)志物。
[Abstract]:Gastric cancer is a serious threat to human health, multifactorial and complex disease, the incidence of cancer in the world second only to lung cancer, breast cancer. Although the surgical treatment of gastric cancer has been improved with the progress of science and technology, the early symptoms of the disease are not obvious, and it is not easy to attract people's attention. As a result, people have developed to the late stage at the time of seeing a doctor, so that the 5-year survival rate of the disease is only 20-30%. In order to improve the level of early diagnosis and prevention of gastric cancer, it is very important to search for reliable molecular markers related to gastric cancer. The Wnt signaling pathway plays a very important role in the carcinogenesis of gastric cancer. The abnormal expression of some suppressor genes in this pathway may activate the pathway and lead to the occurrence of gastric cancer. In this study, we studied the expression of some inhibitory genes (DKK1, DK2, DKK3, SFRP5, SFRP4AXIN2APC) in the Wnt signaling pathway and analyzed the correlation between the expression level and pathological parameters in order to find out the tumor molecular markers for the diagnosis and prevention of gastric cancer. So as to provide a certain reference for early judgment and clinical prediction of gastric cancer. In the experiment, 40 cases of cancer and adjacent tissues were collected. The expression of Wnt suppressor gene was detected by RT-PCR Taqman probe method, and then the expression data were processed by 2-Act and 2ct formula. Finally, the expression data and clinicopathological data were statistically analyzed. The main conclusions of this study were as follows: after Mann-Whitney single tail nonparametric rank sum test, it was found that the relative expression of DKK2 (P0.0001) / SFRP2 (P0. 049) / SFRP5 (P0. 004) gene in gastric carcinogenesis was significantly lower than that of DKK1, DKK3SFRP4, AXIN2APC5 gene in two kinds of tissues. The results of nonparametric rank sum test showed that the expression of DKK2 / SFRP2 / SFRP5 gene was significantly down-regulated in gastric cancer compared with other genes in this pathway, and the results of nonparametric rank sum test showed that the expression of these three genes in gastric cancer was significantly down-regulated than that of other genes in this pathway, and the results of nonparametric rank sum test showed that the expression of these three genes in gastric cancer was significantly lower than that of other genes in this pathway. These three genes may play a more important role in the activation of the pathway. T test analysis showed that the differential expression of the eight genes had no relationship with age, sex and differentiation. However, the expression level of DKKK1, DKK2, DKK3, SFRP2 and SFRP4APC was significantly correlated with the clinical stage of the patients, and the abnormal expression of all inhibitors was statistically significant with the lymph node metastasis of the patients. In conclusion, the abnormal expression of Wnt signaling pathway suppressor gene plays an important role in the carcinogenesis of gastric cancer. The down-regulation of related genes is closely related to the occurrence and progression of gastric cancer, which may be used as a molecular marker for early diagnosis of gastric cancer.
【學(xué)位授予單位】：西北大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R735.2

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 龍文;;胃癌術(shù)后復(fù)發(fā)19例臨床研究[J];現(xiàn)代診斷與治療;2013年02期

2 呂承福;一例胃癌晚期患者因意外傷害而痊愈的啟示[J];針灸臨床雜志;1996年04期

3 王璦萍,田衛(wèi)衛(wèi);胃癌并心包轉(zhuǎn)移1例[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2000年13期

4 王健,鄒義壯,唐麗麗,李杰,張東,金山,劉娟;胃癌患者的生存期與個性特征、應(yīng)付方式及免疫功能的相關(guān)性研究[J];中華精神科雜志;2001年03期

5 王博文,楊波,趙淑琴;青年胃癌33例臨床分析[J];寧夏醫(yī)學(xué)雜志;2002年10期

6 劉步珍,張海芳;以胃外表現(xiàn)為首發(fā)癥狀的胃癌26例誤診分析[J];山東醫(yī)藥;2003年18期

7 任剛,蔡嶸,陳強,許幼如,程普選,陳惠芳;女性胃癌[J];上海醫(yī)學(xué);2003年03期

8 王盛根,王壽九,吳楠,潘桂紅,焦霞;母子同時患胃癌報告[J];臨床腫瘤學(xué)雜志;2004年01期

9 徐開,陳連珠;1例胃癌晚期術(shù)后使用苦草治療[J];現(xiàn)代醫(yī)藥衛(wèi)生;2004年24期

10 唐建榮;;胃癌患者192例首診漏誤診分析[J];中國臨床醫(yī)生;2007年03期

相關(guān)會議論文 前4條

1 張恩寧;;胃癌[A];山東省第四屆“CSCO——山東”首屆腫瘤化療學(xué)習(xí)班論文匯編[C];2009年

2 徐智民;周丹;張萬岱;何燕萍;智發(fā)朝;朱建新;王莉慧;肖冰;潘德壽;宋姍;趙永玲;;幽門螺桿菌感染及其免疫型與胃癌的關(guān)系研究[A];中國中西醫(yī)結(jié)合學(xué)會第十四次全國消化系統(tǒng)疾病學(xué)術(shù)研討會論文匯編[C];2002年

3 魏品康;;胃癌非手術(shù)療法治療研究與策略[A];中國中西醫(yī)結(jié)合學(xué)會第十六次全國消化系統(tǒng)疾病學(xué)術(shù)研討會論文匯編[C];2004年

4 郭新海;毛芙敏;吳旭輝;許敬;凌志強;李繼承;;舟山海島地區(qū)胃癌D17S396基因遺傳不穩(wěn)定性與胃癌的淋巴轉(zhuǎn)移[A];2009年浙江省腫瘤學(xué)術(shù)年會暨腫瘤診治新進展學(xué)習(xí)班論文匯編[C];2009年

相關(guān)重要報紙文章 前10條

1 天津市腫瘤醫(yī)院 梁寒;五類人警惕胃癌[N];大眾衛(wèi)生報;2007年

2 本報記者 項煜虹;胃癌正襲向習(xí)慣不良的年輕人群[N];大眾科技報;2008年

3 天津醫(yī)科大學(xué)腫瘤醫(yī)院胃部腫瘤科教授 梁寒　整理 李運紅 胡顏;胃癌盯上中堅力量[N];健康報;2008年

4 本報記者 劉學(xué)美;警惕胃癌[N];中國消費者報;2000年

5 ;胃癌晚期能活多久[N];大眾衛(wèi)生報;2010年

6 本報記者　朱勤;三代教授破解“莊河之謎”[N];遼寧日報;2006年

7 ;胃癌:隱蔽的殺手[N];醫(yī)藥經(jīng)濟報;2005年

8 健康時報記者 劉永曉　特約記者 施敏;胃癌新晉青年殺手[N];健康時報;2011年

9 趙迎 任勇;胃癌襲向年輕人[N];天津日報;2006年

10 北京天壇醫(yī)院外科主任 宋茂民;預(yù)防胃癌牢記九點[N];大眾衛(wèi)生報;2006年

相關(guān)博士學(xué)位論文 前10條

1 秦云植;NQO1及其抑制劑在胃癌預(yù)后評估及靶向治療中的作用研究[D];延邊大學(xué);2015年

2 宋宗昌;PRR11在胃癌細(xì)胞增殖與體內(nèi)生長中的作用及其機制研究[D];第三軍醫(yī)大學(xué);2015年

3 石s，

本文編號：2162776