本文選題：胃腫瘤　切入點(diǎn)：PCDH8　出處：《青島大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：胃癌是一種死亡率很高的惡性腫瘤,大部分胃癌患者確診時(shí)已處于晚期階段,早期診斷十分重要。胃癌產(chǎn)生與演變過程極為復(fù)雜,涉及環(huán)境、遺傳等各個(gè)方面,其中DNA甲基化在胃癌發(fā)生過程中發(fā)揮重要作用。PCDH8(protocadherin-8,原鈣粘蛋白-8)是一種新的抑癌基因,是原鈣粘蛋白家族的成員。研究發(fā)現(xiàn),PCDH8基因的表達(dá)減少或缺失受其啟動(dòng)子甲基化的影響,與多種腫瘤關(guān)系密切。研究目的:1.檢測(cè)PCDH8基因在人類胃癌組織及癌旁正常組織中的甲基化狀態(tài),分析PCDH8基因與胃癌TNM分期及是否存在淋巴轉(zhuǎn)移之間的相關(guān)性。2.分析PCDH8與Dnmt1(細(xì)胞內(nèi)甲基轉(zhuǎn)移酶1)兩者之間的相關(guān)性。3.探討PCDH8與Dnmt1在胃癌發(fā)生及發(fā)展過程中發(fā)揮的生物學(xué)作用。研究方法:收集2012年7月-2013年9月在青島大學(xué)醫(yī)學(xué)院附屬青島市市立醫(yī)院普外科行手術(shù)切除的60例胃癌患者的新鮮胃癌組織及其相應(yīng)的癌旁組織標(biāo)本,胃癌組織取自癌灶中央非壞死區(qū)域,癌旁組織取自距離癌組織5cm以上,且術(shù)前未行放療、化療、靶向治療等抗腫瘤治療。通過甲基化特異性聚合酶鏈?zhǔn)椒磻?yīng)(methylationspecific PCR,MSP)的方法檢測(cè)PCDH8基因啟動(dòng)子區(qū)甲基化情況,并分析在60例胃癌組織和其癌旁正常胃粘膜組織中的差異;采用免疫組化SP法檢測(cè)胃癌組織以及相應(yīng)的癌旁組織中PCDH8基因蛋白及Dnmt1蛋白的表達(dá)水平,綜合分析PCDH8及Dnmt1表達(dá)與胃癌的關(guān)系,并對(duì)胃癌中PCDH8基因甲基化及Dnmt1蛋白表達(dá)的關(guān)系進(jìn)行初步探討。結(jié)果:PCDH8甲基化的陽(yáng)性表達(dá)率在癌旁正常胃粘膜組織中僅為3.3%(2/60),而PCDH8甲基化的陽(yáng)性表達(dá)率在胃癌組織中為55.0%(33/60),差異具有統(tǒng)計(jì)學(xué)意義(χ2=38.76,p0.001);胃癌患者腫瘤組織中PCDH8的甲基化率與是否存在淋巴結(jié)轉(zhuǎn)移的差異具有統(tǒng)計(jì)學(xué)的意義(χ2=17.47,p0.001),而與腫瘤的TNM分期以及病人的年齡、性別等差異均沒有統(tǒng)計(jì)學(xué)意義(p均0.05)。PCDH8蛋白在胃癌組織的表達(dá)率(11.7%)遠(yuǎn)遠(yuǎn)低于其在癌旁正常胃粘膜組織中的表達(dá)率(90.0%)(χ2=73.65,p0.001),而癌旁正常胃粘膜組織中Dnmt1蛋白的陽(yáng)性表達(dá)率(5.0%)明顯低于胃癌組織中Dnmt1蛋白的陽(yáng)性表達(dá)率(73.3%)(χ2=58.79,p0.001)。在胃癌組織中檢測(cè)的PCDH8蛋白與Dnmt1蛋白的表達(dá)呈負(fù)相關(guān)(r=-0.544,p0.001)。結(jié)論:PCDH8基因在胃癌組織中呈低表達(dá),DNMT1在癌組織中高表達(dá),表明其可能與胃癌發(fā)生關(guān)系密切。PCDH8基因甲基化以及Dnmt1表達(dá)的增高可能參與了胃癌的發(fā)生和發(fā)展過程。胃癌組織中DNMT1的蛋白的高表達(dá),可能導(dǎo)致抑癌基因PCDH8基因啟動(dòng)子區(qū)發(fā)生異常甲基化,使抑癌基因蛋白表達(dá)減少,失去了對(duì)腫瘤發(fā)生的抑制作用。
[Abstract]:Gastric cancer is a kind of malignant tumor with high mortality. Most patients with gastric cancer are in advanced stage by the time of diagnosis. Early diagnosis is very important. The process of gastric cancer production and evolution is very complicated, involving various aspects such as environment, heredity and so on. Among them, DNA methylation plays an important role in gastric carcinogenesis. PCDH8- 8 (procalcitonin -8) is a new tumor suppressor gene and a member of procadherin family. It has been found that the decreased or missing expression of PCDH8 gene is affected by its promoter methylation. Objective: 1. To detect the methylation status of PCDH8 gene in human gastric cancer tissues and adjacent normal tissues. To analyze the correlation between PCDH8 gene and TNM stage and lymphatic metastasis of gastric cancer. 2. To analyze the correlation between PCDH8 and Dnmt1 (intracellular methyltransferase 1). 3. To study the relationship between PCDH8 and Dnmt1 in the development and development of gastric cancer. Methods: from July 2012 to September 2013, fresh gastric cancer tissues and corresponding adjacent tissues were collected from 60 patients with gastric cancer who underwent surgical resection in general surgery, Qingdao Municipal Hospital affiliated to Qingdao University Medical College, from July 2012 to September 2013. The tissues of gastric cancer were taken from the non-necrotic area in the center of the cancer focus, and the adjacent tissues were taken from the tissues more than 5 cm from the cancerous tissue, and they were not treated with radiotherapy and chemotherapy before operation. Methylation specific polymerase chain reaction (methylation specific polymerase chain reaction) was used to detect methylation of promoter region of PCDH8 gene, and the difference was analyzed in 60 cases of gastric cancer and its adjacent normal gastric mucosa. Immunohistochemical SP method was used to detect the expression of PCDH8 gene protein and Dnmt1 protein in gastric cancer tissues and adjacent tissues. The relationship between PCDH8 and Dnmt1 expression and gastric cancer was analyzed. The relationship between the methylation of PCDH8 gene and the expression of Dnmt1 protein in gastric cancer was studied. Results the positive rate of methylation of PCDH8 gene in normal gastric mucosa adjacent to gastric cancer was only 3.3 / 60%, while the positive rate of PCDH8 methylation in gastric cancer tissue was 3.3 / 60%. The difference was statistically significant (蠂 2: 38.76%, p 0.001). The methylation rate of PCDH8 was significantly different from the presence of lymph node metastasis in gastric cancer (蠂 2 + 17.47%, p 0.001), but the TNM stage of the tumor and the age of the patient were statistically significant (蠂 2 / 17. 47%, P 0. 001, P 0. 001, P < 0. 05), and the difference was statistically significant (蠂 2 + 17. 47%, P 0. 001). The expression rate of PCDH8 protein in gastric cancer tissues was significantly lower than that in adjacent normal gastric mucosa tissues. (蠂 2 + 73.65%, p 0.001), and the positive expression rate of Dnmt1 protein in adjacent normal gastric mucosa tissues was 5.0% (P < 0.05). The positive expression rate of Dnmt1 protein in gastric cancer was significantly lower than that in gastric carcinoma (蠂 2 / 58.79 / p 0.001). There was a negative correlation between the expression of PCDH8 protein and Dnmt1 protein in gastric cancer tissue. Conclusion the low expression of DNMT1 gene was found in gastric cancer tissue. It is suggested that the methylation of PCDH8 gene and the increase of Dnmt1 expression may be involved in the carcinogenesis and progression of gastric cancer. It may lead to abnormal methylation in the promoter of tumor suppressor gene PCDH8 gene and decrease the expression of tumor suppressor gene protein.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R735.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 董曉波;;體育鍛煉與膳食干預(yù)對(duì)超重肥胖大學(xué)生體質(zhì)的影響研究[J];浙江體育科學(xué);2015年03期

2 John C.Layke;Peter P.Lopez;本刊編輯部;;胃癌:診斷和治療方案的選擇[J];中國(guó)全科醫(yī)學(xué);2015年03期

3 孫宇;李蕊;趙紅;;孕前超重肥胖者早期飲食運(yùn)動(dòng)干預(yù)對(duì)孕期體質(zhì)量增長(zhǎng)的影響研究[J];護(hù)理學(xué)報(bào);2014年24期

4 于云鵬;李長(zhǎng)嚴(yán);黃冠男;姜相君;;胃癌組織中PCDH8基因甲基化及Dnmt1表達(dá)的關(guān)系[J];中國(guó)癌癥防治雜志;2014年03期

5 王倩;唐維平;;DNMT1與DNA異常甲基化及腫瘤的關(guān)系[J];重慶醫(yī)學(xué);2014年17期

6 吳明亮;管同郁;林英立;吳剛;戚景光;;膀胱癌組織中PCDH8基因啟動(dòng)子甲基化狀態(tài)及其臨床意義[J];重慶醫(yī)學(xué);2014年01期

7 季加孚;;我國(guó)胃癌防治研究三十年回顧[J];中國(guó)腫瘤臨床;2013年22期

8 石宇良;曾泉;龍表利;向庭秀;洪蘇玲;胡國(guó)華;;PCDH8基因表達(dá)對(duì)鼻咽癌細(xì)胞生物學(xué)效應(yīng)的影響[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2013年14期

9 姜相君;初蕾蕾;崔艷欣;宋明全;解祥軍;田字彬;;Runx3、Rassf1a基因啟動(dòng)子在胃癌組織中的高甲基化及Dnmt1的表達(dá)[J];世界華人消化雜志;2012年35期

10 鄔雪山;孫桂平;秦新紅;;以健康教育為主綜合干預(yù)對(duì)超重、肥胖及高血壓影響分析[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2012年32期

，

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