本文選題：食管鱗癌 + 賁門(mén)腺癌��； 參考：《河北醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:食管癌(esophageal cancer,EC)是最常見(jiàn)的消化系統(tǒng)惡性腫瘤之一,在全球有較高死亡率。EC的發(fā)生有明顯地區(qū)差異,中國(guó)食管癌的發(fā)病率明顯高于其他國(guó)家。其中食管鱗狀細(xì)胞癌(esophageal squamous cell carcinoma,ESCC)是EC的主要病理類(lèi)型。盡管近年來(lái),ESCC在多學(xué)科綜合治療中取得了一定的效果,但5年生存率仍然很低。賁門(mén)腺癌(gastric cardia adenocarcinoma,GCA)是我國(guó)北方地區(qū)較為常見(jiàn)的惡性腫瘤之一。GCA起病隱匿且其發(fā)病率總體呈上升趨勢(shì),有癥狀來(lái)就診時(shí)患者多數(shù)已到中晚期。然而迄今為止,食管鱗癌和賁門(mén)腺癌的發(fā)病機(jī)制尚未完全明確。因此,尋找ESCC及GCA發(fā)生的早期生物標(biāo)志物,探索其發(fā)病機(jī)制對(duì)于臨床中的預(yù)防及治療顯得尤為重要。長(zhǎng)鏈非編碼RNA(long non-coding RNA,lnc RNAs)是指長(zhǎng)度在200~100000 nt之間,具有調(diào)控基因表達(dá)作用的非編碼RNA。近年來(lái)研究者通過(guò)基因芯片技術(shù)篩選出的lnc RNAs在ESCC及GCA發(fā)病中的作用機(jī)制仍不清楚,lnc RNAs與ESCC、GCA相關(guān)性的研究報(bào)道較少。因此,本研究旨在通過(guò)檢測(cè)lnc RNA LOC100130476在食管癌細(xì)胞系、食管鱗癌及賁門(mén)腺癌組織中的表達(dá)情況及甲基化狀態(tài),分析該lnc RNA表達(dá)與甲基化狀態(tài)的相關(guān)性,并結(jié)合臨床資料探討其與患者年齡、性別、淋巴結(jié)轉(zhuǎn)移、組織分化程度、TNM分期之間的關(guān)系,為lnc RNA LOC100130476在ESCC及GCA發(fā)生和發(fā)展中的作用提供實(shí)驗(yàn)依據(jù)。方法:1應(yīng)用反轉(zhuǎn)錄-聚合酶鏈反應(yīng)(reverse transcription-polymerase chain reaction,RT-PCR)法分別檢測(cè)DNA甲基轉(zhuǎn)移酶抑制劑5-氮雜-2’-脫氧胞苷(5-aza-2’-deoxycitydine,5-Aza-d C)處理前后的食管癌細(xì)胞系(TE1、TE13、T.Tn、Eca109)中、72例食管鱗癌及相應(yīng)癌旁正常組織中和76例賁門(mén)腺癌及相應(yīng)癌旁正常組織中LOC100130476的表達(dá)情況。2應(yīng)用甲基化特異性聚合酶鏈反應(yīng)(methylation specific polymerasechain reaction,MSP)法分別檢測(cè)應(yīng)用5-Aza-d C處理前后的食管癌細(xì)胞系、72例食管鱗癌及相應(yīng)癌旁正常組織中和76例賁門(mén)腺癌及相應(yīng)癌旁正常組織中LOC100130476的甲基化狀態(tài)。3運(yùn)用統(tǒng)計(jì)學(xué)軟件SPSS13.0對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果:1食管癌細(xì)胞系中l(wèi)nc RNA LOC100130476的表達(dá)情況及甲基化狀態(tài)1食管癌細(xì)胞系中l(wèi)nc RNA LOC100130476的表達(dá)情況及甲基化狀態(tài)1.1 5-Aza-d C處理前后食管癌細(xì)胞系中l(wèi)nc RNA LOC100130476的表達(dá)未經(jīng)5-Aza-dC處理的食管癌TE1、TE13和T.Tn細(xì)胞中LOC100130476的表達(dá)均為陰性,在Eca109細(xì)胞中為弱陽(yáng)性表達(dá);用5-Aza-d C處理后,TE1、TE13和T.Tn細(xì)胞中LOC100130476均轉(zhuǎn)變?yōu)殛?yáng)性表達(dá),而在Eca109細(xì)胞中較未用5-Aza-d C處理的細(xì)胞表達(dá)上調(diào)。1.2 5-Aza-d C處理前后的食管癌細(xì)胞系中l(wèi)nc RNA LOC100130476的甲基化狀態(tài)TE1、TE13、T.Tn和Eca109細(xì)胞中,在5-Aza-d C未處理前LOC100130476均表現(xiàn)為高甲基化的狀態(tài),應(yīng)用5-Aza-d C處理后,Eca109細(xì)胞系中LOC100130476甲基化程度明顯降低,其余3種細(xì)胞中的LOC100130476則均表現(xiàn)為非甲基化狀態(tài)。2食管鱗癌組織中l(wèi)nc RNA LOC100130476的表達(dá)水平、甲基化狀態(tài)以及與臨床病理學(xué)資料之間的關(guān)系2.1食管鱗癌組織中l(wèi)nc RNA LOC100130476的表達(dá)LOC100130476在食管鱗癌組織中的表達(dá)顯著低于相應(yīng)癌旁正常組織(0.49±0.09 vs 0.56±0.08),兩者差異具有統(tǒng)計(jì)學(xué)意義(t=-5.893,P0.05)。在食管鱗癌患者中,LOC100130476的表達(dá)與組織分化程度和TNM分期密切相關(guān)(P0.05),而與患者的年齡、性別以及淋巴結(jié)轉(zhuǎn)移無(wú)關(guān)(P0.05)。2.2食管鱗癌組織中l(wèi)nc RNA LOC100130476的甲基化狀態(tài)食管鱗癌組織中LOC100130476的第一外顯子區(qū)甲基化率顯著高于癌旁正常組織[69.4%(50/72)vs 26.4%(19/72)],兩者差異具有統(tǒng)計(jì)學(xué)意義(χ2=26.741,P0.05),并與組織分化程度和TNM分期密切相關(guān)(P0.05),而與患者的年齡、性別以及淋巴結(jié)轉(zhuǎn)移無(wú)關(guān)(P0.05)。發(fā)生LOC100130476甲基化的食管鱗癌組織中LOC100130476的表達(dá)顯著低于未發(fā)生甲基化的食管鱗癌組織(0.47±0.08 vs 0.55±0.08),兩者差異具有統(tǒng)計(jì)學(xué)意義(t=-4.099,P0.05)。3賁門(mén)腺癌組織中l(wèi)nc RNA LOC100130476的表達(dá)水平、甲基化狀態(tài)以及與臨床病理學(xué)資料之間的關(guān)系3.1賁門(mén)腺癌組織中l(wèi)nc RNA LOC100130476的表達(dá)LOC100130476在賁門(mén)腺癌組織中的表達(dá)顯著低于相應(yīng)癌旁正常組織(0.61±0.22 vs 0.79±0.23),兩者差異具有統(tǒng)計(jì)學(xué)意義(t=-5.387,P0.05)。在賁門(mén)腺癌患者中,LOC100130476的表達(dá)與組織分化程度和淋巴結(jié)轉(zhuǎn)移密切相關(guān)(P0.05),而與患者的年齡、性別以及TNM分期無(wú)關(guān)(P0.05)。3.2賁門(mén)腺癌組織中l(wèi)nc RNA LOC100130476的甲基化狀態(tài)賁門(mén)腺癌組織中LOC100130476的第一外顯子區(qū)甲基化率顯著高于癌旁正常組織[64.5%(49/76)vs 23.7%(18/76)],兩者差異具有統(tǒng)計(jì)學(xué)意義(χ2=25.649,P0.05),并與組織分化程度和淋巴結(jié)轉(zhuǎn)移密切相關(guān)(P0.05),而與患者的年齡、性別以及TNM分期無(wú)關(guān)(P0.05)。發(fā)生LOC100130476甲基化的賁門(mén)腺癌組織中LOC100130476的表達(dá)顯著低于未發(fā)生甲基化的賁門(mén)腺癌組織(0.56±0.21 vs 0.71±0.21),兩者差異具有統(tǒng)計(jì)學(xué)意義(t=-3.055,P0.05)。結(jié)論:1 LOC100130476與食管鱗癌、賁門(mén)腺癌的發(fā)生、發(fā)展密切相關(guān),并可能起抑癌基因的作用。2 LOC100130476第一外顯子區(qū)甲基化異常增高可能是導(dǎo)致其表達(dá)下調(diào)的機(jī)制之一。3 LOC100130476第一外顯子區(qū)甲基化狀態(tài)可能與食管鱗癌、賁門(mén)腺癌的惡性程度及進(jìn)展相關(guān)。
[Abstract]:Objective: esophageal cancer (EC) is one of the most common malignant tumors of the digestive system. There is a significant regional difference in the incidence of.EC in the world. The incidence of esophageal cancer in China is obviously higher than that of other countries. The main pathological type of EC is esophageal squamous cell carcinoma (esophageal squamous cell carcinoma, ESCC). In recent years, ESCC has achieved a certain effect in the multidisciplinary integrated treatment, but the 5 year survival rate is still very low. Gastric cardia adenocarcinoma (GCA) is one of the most common malignant tumors in northern China..GCA is insidious and its incidence is generally on the rise. Most of the patients have come to the middle and late stages when they have symptoms. So far, the pathogenesis of esophageal squamous and cardiac adenocarcinoma is not completely clear. Therefore, it is particularly important to find the early biomarkers of ESCC and GCA and explore its pathogenesis for the prevention and treatment of clinical. Long chain non coded RNA (long non-coding RNA, LNC RNAs) refers to the length between 200~100000 nt and modulation. The mechanism of non coding RNA. for controlling gene expression in recent years is not clear in the pathogenesis of LNC RNAs screened by gene chip technology in the pathogenesis of ESCC and GCA. There are few reports on the correlation between LNC RNAs and ESCC and GCA. Therefore, this study aims to detect LNC RNA LOC100130476 in esophageal cancer cell lines, esophageal squamous cell carcinoma and cardiac glands. The expression and methylation status of the cancer tissue were analyzed, and the correlation between the expression of LNC RNA and methylation status was analyzed, and the relationship between the age, sex, lymph node metastasis, the degree of tissue differentiation, TNM staging and the effect of LNC RNA LOC100130476 on the occurrence and development of ESCC and GCA were provided. Method: 1 the reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the esophageal cancer cell lines before and after the DNA methyltransferase inhibitor 5- aza -2 'deoxycytidine (5-Aza-2' -deoxycitydine, 5-Aza-d C), and 72 cases of esophageal squamous cell carcinoma and the corresponding normal paracancerous group. Expression of LOC100130476 in 76 cases of gastric cardia adenocarcinoma and corresponding normal tissue adjacent to cancer.2 using methylation specific polymerase chain reaction (methylation specific polymerasechain reaction, MSP) to detect esophageal cancer cell lines before and after 5-Aza-d C treatment, 72 cases of esophageal squamous cell carcinoma and 76 cases of corresponding normal tissue adjacent to cancer. Methylation status of LOC100130476 in gastric cardia adenocarcinoma and corresponding normal tissue.3 using statistical software SPSS13.0 to analyze the data. Results: the expression of LNC RNA LOC100130476 in 1 esophageal carcinoma cell lines and methylation status, the expression of LNC RNA LOC100130476 in 1 esophageal cancer cell lines and methylation status 1.1 5-Az The expression of LNC RNA LOC100130476 in esophageal cancer cell lines before and after A-D C treatment was negative in TE1, TE13 and T.Tn cells in TE1, TE13 and T.Tn cells, and was weakly positive in Eca109 cells. The methylation status of LNC RNA LOC100130476 in esophageal cancer cell lines before and after.1.2 5-Aza-d C treatment was up before and after.1.2 5-Aza-d C treatment. The methylation status of LNC RNA LOC100130476 in TE13, T.Tn and Eca109 cells The degree of LOC100130476 in the other 3 cells showed the expression level of LNC RNA LOC100130476 in the non methylation state of.2 esophageal squamous cell carcinoma, the methylation status and the relationship with the clinicopathological data. 2.1 the expression of LOC100130476 in esophageal squamous cell carcinoma tissue in the esophageal squamous cell carcinoma tissue The expression was significantly lower than that of the normal tissues adjacent to the carcinoma (0.49 + 0.09 vs 0.56 + 0.08). The difference was statistically significant (t=-5.893, P0.05). In the patients with esophageal squamous cell carcinoma, the expression of LOC100130476 was closely related to the degree of tissue differentiation and TNM staging (P0.05), but was not related to the age, sex, and lymph node metastasis of the patients (P0.05).2.2 esophageal squamous cell carcinoma group. The methylation status of LNC RNA LOC100130476 in the tissue of the tissue was significantly higher than that of [69.4% (50/72) vs 26.4% (19/72) in the normal tissue adjacent to the normal tissue of the carcinoma of the esophagus. The difference was statistically significant (x 2=26.741, P0.05), and was closely related to the degree of tissue differentiation and TNM (P0.05), and the age of the patients. Sex and lymph node metastasis were not related (P0.05). The expression of LOC100130476 in the tissue of LOC100130476 methylation of esophageal squamous cell carcinoma was significantly lower than that of non methylation esophageal squamous cell carcinoma (0.47 + 0.08 vs 0.55 + 0.08). The difference was statistically significant (t=-4.099, P0.05) the expression level of LNC RNA LOC100130476 in.3 cardiac adenocarcinoma tissue The relationship between methylation and clinicopathological data in 3.1 cardiac adenocarcinoma tissue, expression of LNC RNA LOC100130476 in gastric cardia adenocarcinoma was significantly lower than that of normal tissues adjacent to the carcinoma (0.61 + 0.22 vs 0.79 + 0.23), and the difference was statistically significant (t=-5.387, P0.05). In the patients with cardiac adenocarcinoma, LO The expression of C100130476 is closely related to the degree of tissue differentiation and lymph node metastasis (P0.05), but not with the age, sex, and TNM staging of the patients (P0.05) the methylation of LNC RNA LOC100130476 in the.3.2 cardiac adenocarcinoma tissue of.3.2, the methylation rate of the first exon of the LOC100130476 in the gastric cardia adenocarcinoma tissue is significantly higher than that of the normal tissue adjacent to the carcinoma [64.5%. (49/76) vs 23.7% (18/76)], the differences were statistically significant (x 2=25.649, P0.05), closely related to the degree of tissue differentiation and lymph node metastasis (P0.05), but not with age, sex, and TNM staging (P0.05). The expression of LOC100130476 in the cardiac adenocarcinoma tissue with LOC100130476 methylation was significantly lower than that of non methylation. The difference of cardiac adenocarcinoma (0.56 + 0.21 vs 0.71 + 0.21) was statistically significant (t=-3.055, P0.05). Conclusion: 1 LOC100130476 is closely related to the development of carcinoma of the esophagus, gastric cardia adenocarcinoma, and may play the role of tumor suppressor gene in.2 LOC100130476 first exon methylation The methylation status of the first exon region of.3 LOC100130476 may be related to the malignancy and progression of esophageal squamous cell carcinoma and cardiac adenocarcinoma.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R735

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