本文選題：宮頸癌 + 葉酸��； 參考：《山西醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：宮頸癌是女性最常見(jiàn)的婦科惡性腫瘤之,發(fā)病率呈逐年上升趨勢(shì)。高危型人乳頭瘤病毒(HR-HPV)感染是宮頸癌發(fā)生的重要病因,但并非唯一因素,故尋找HR-HPV感染的協(xié)同因素在阻斷ClN進(jìn)展為宮頸癌的過(guò)程中非常重要。宮頸癌的發(fā)生、發(fā)展是多因素、多步驟、長(zhǎng)時(shí)間作用的結(jié)果,是一個(gè)及其復(fù)雜的生物學(xué)過(guò)程。目前最新研究發(fā)現(xiàn),microRNA的異常表達(dá)及葉酸缺乏與宮頸癌的發(fā)生密切相關(guān),而其具體機(jī)制尚不清楚。故本研究的目的在于：1.檢測(cè)宮頸病變組織中miR-203的表達(dá)狀態(tài),探討其在宮頸病變發(fā)生發(fā)展中的作用。2.體外不同濃度葉酸干預(yù)下檢測(cè)宮頸癌Caski細(xì)胞中mi R-203的甲基化狀態(tài)、mi R-203的表達(dá)水平,探討葉酸缺乏致宮頸癌發(fā)生的可能機(jī)制。方法：1.研究對(duì)象選取2012年1月至2013年1月于我院婦科門(mén)診就診行陰道鏡檢查的90例患者,根據(jù)陰道鏡宮頸活檢病理診斷結(jié)果分為子宮頸上皮內(nèi)瘤變(CIN)30例,鱗狀細(xì)胞癌(SCC)30例作為研究組;宮頸組織病理學(xué)結(jié)果正常30例作為對(duì)照組。2.取患者的宮頸組織,RT-PCR技術(shù)檢測(cè)90例患者宮頸組織中mi R-203的表達(dá)水平。3.常規(guī)培養(yǎng)宮頸癌Caski細(xì)胞株,取對(duì)數(shù)生長(zhǎng)期的細(xì)胞,給予不同濃度的葉酸干預(yù)后,采用甲基化特異性PCR(MSP)法檢測(cè)不同葉酸濃度組宮頸癌細(xì)胞中miR-203的甲基化狀態(tài),RT-PCR法檢測(cè)不同葉酸濃度組宮頸癌細(xì)胞中miR-203的表達(dá)水平。4.采用SPSS 16.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,定量資料的多組間比較采用單因素方差分析,組間的多重比較采用LSD-t檢驗(yàn),率的比較采用X2檢驗(yàn),相關(guān)性分析采用Spearman秩相關(guān),以P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果：1.正常宮頸組織、CIN組織、宮頸癌組織中miR-203的相對(duì)表達(dá)量分別為1.00±0.10,0.13±0.03,0.27±0.05。各組miR-203的表達(dá)量比較采用單因素方差分析,miR-203的表達(dá)量差異有統(tǒng)計(jì)學(xué)意義(F=6.414,P=0.005)。各組miR-203的表達(dá)量的組間比較采用LSD-t檢驗(yàn),正常組與CIN組間miR-203的表達(dá)量差別有統(tǒng)計(jì)學(xué)意義(P=0.001),正常組與宮頸癌組、CIN組與宮頸癌組miR-203的表達(dá)差別無(wú)統(tǒng)計(jì)學(xué)意義(P=0.151,P=0.060)。2.不同葉酸組宮頸癌細(xì)胞中,隨著葉酸水平的升高,mi R-203的CpG島甲基化率呈下降趨勢(shì)(X2=27.473, P0.001), miR-203的表達(dá)水平呈上升趨勢(shì)(F=427.416,P0.001)。對(duì)miR-203的CpG島甲基化率與miR-203的表達(dá)水平進(jìn)行相關(guān)性分析,呈負(fù)相關(guān)(rs=-0.886,P=0.019)。結(jié)論：1.在宮頸病變組織中較宮頸正常組織,miR-203的表達(dá)水平下調(diào),miR-203表達(dá)水平的下調(diào)可能參與了宮頸癌的發(fā)生。2.葉酸缺乏可能會(huì)通過(guò)導(dǎo)致miR-203高甲基化,使其表達(dá)水平下調(diào),進(jìn)而在宮頸癌變過(guò)程中發(fā)揮一定作用。
[Abstract]:Objective: cervical cancer is the most common gynecologic malignant tumor in women, the incidence is increasing year by year. High-risk human papillomavirus (HR-HPV) infection is an important cause of cervical cancer, but it is not the only factor, so it is very important to search for co-factors of HR-HPV infection in the process of blocking the progression of ClN to cervical cancer. The occurrence and development of cervical cancer is the result of multi-factor, multi-step and long-term action, which is an extremely complicated biological process. Recent studies have found that the abnormal expression of microRNA and folic acid deficiency are closely related to the occurrence of cervical cancer, but its mechanism is not clear. Therefore, the purpose of this study is to 1: 1. To detect the expression of miR-203 in cervical lesions and to explore its role in the occurrence and development of cervical lesions. The methylation status of mi R-203 in cervical cancer Caski cells was detected by different concentrations of folic acid in vitro, and the possible mechanism of carcinogenesis induced by folic acid deficiency was discussed. Method 1: 1. From January 2012 to January 2013, 90 patients underwent colposcopy examination in gynecological outpatient clinic of our hospital. According to the pathological diagnosis results of colposcopy cervical biopsy, 30 cases of cervical intraepithelial neoplasia and 30 cases of squamous cell carcinoma (SCC) were divided into two groups: 30 cases of cervical intraepithelial neoplasia and 30 cases of squamous cell carcinoma (SCC). Cervical histopathological results were normal in 30 cases as control group. 2. 2. The expression level of mi R-203 was detected by RT-PCR in cervical tissues of 90 patients. Caski cell lines of cervical cancer were cultured routinely. The cells in logarithmic growth period were treated with folic acid at different concentrations. The methylation status of miR-203 in cervical cancer cells with different folic acid concentration was detected by methylation specific PCR. RT-PCR was used to detect the expression level of miR-203 in cervical cancer cells with different folic acid concentration. Statistical software SPSS 16.0 was used for statistical analysis. The multivariate analysis of variance was used in the comparison of quantitative data, the LSD-t test was used for the multiple comparison of the quantitative data, the X2 test was used for the rate comparison, and the Spearman rank correlation was used for the correlation analysis. P0.05 as the difference was statistically significant. The result is 1: 1. The relative expression of miR-203 in normal cervical tissues and cervical carcinoma tissues was 1.00 鹵0.10 鹵0.13 鹵0.03 鹵0.27 鹵0.05, respectively. The expression of miR-203 in each group was compared by univariate analysis of variance (ANOVA). LSD-t test was used to compare the expression of miR-203 in each group. There was significant difference in the expression of miR-203 between normal group and CIN group. There was no significant difference in miR-203 expression between normal group and cervical carcinoma group (cin group and cervical cancer group). There was no significant difference in miR-203 expression between normal group and cervical cancer group. With the increase of folic acid level, the methylation rate of CpG islands in different folic acid groups decreased with the increase of folic acid level in cervical cancer cells. The expression level of miR-203 was increased with the increase of the level of folic acid in the cervical cancer cells (P _ (0.001) and X _ (2) ~ (2) O _ (27.416) P _ (0.001) (P _ (0.001). The correlation between CpG island methylation rate and miR-203 expression in miR-203 was negatively correlated with that of miR-203. Conclusion 1. The down-regulation of miR-203 expression level in cervical lesions may be involved in the occurrence of cervical cancer. Folic acid deficiency may play a role in the process of cervical cancer by inducing hypermethylation of miR-203 and down-regulation of its expression.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R737.33

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