【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(jìn)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?cè)诰驮\時(shí)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(hào)通路對(duì)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(huì)使該通路活化,導(dǎo)致胃癌發(fā)生。因此本實(shí)驗(yàn)主要通過對(duì)Wnt信號(hào)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(shí)驗(yàn)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(duì)表達(dá)數(shù)據(jù)進(jìn)行處理,最后將表達(dá)數(shù)據(jù)與臨床病理數(shù)據(jù)進(jìn)行統(tǒng)計(jì)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(yàn)后,發(fā)現(xiàn)DKK2(P0.0001)、SFRP2(P=0.049)、SFRP5(P=0.004)3個(gè)基因在胃癌發(fā)生中表達(dá)水平明顯降低,；DKK1、DKK3、、SFRP4、、AXIN2、APC5個(gè)基因在兩類組織中的相對(duì)表達(dá)沒有明顯差異,說明DKK2、SFRP2、SFRP5這3個(gè)基因的表達(dá)下調(diào),對(duì)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(yàn)結(jié)果顯示,在胃癌中DKK、SFRP2、SFRP5這3個(gè)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(gè)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(yàn)分析發(fā)現(xiàn),這8個(gè)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(gè)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(jì)學(xué)上也具有顯著性。綜上所述,Wnt信號(hào)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(jìn)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(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R735.2

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