本文選題：SHOX2 + GSTP1��； 參考：《山西醫(yī)科大學》2014年碩士論文

【摘要】：背景：前列腺癌（PCa）是歐美發(fā)達國家男性發(fā)病率最高的惡性腫瘤，死亡率也較高。PCa在我國的發(fā)病率較歐美低，但近年來，我國PCa的發(fā)病率呈現(xiàn)明顯上升趨勢。對于早期發(fā)現(xiàn)的局灶性PCa的患者進行PCa根治手術(shù)是最好的治療手段,愈后理想。PCa檢測的目標就在于能夠在疾病的早期明確診斷。因此，尋找PCa早期腫瘤標志物成為泌尿外科臨床醫(yī)師急需解決的問題。目前，血清前列腺特異性抗原（PSA）作為PCa的單一檢測指標，雖然具有較高的PCa陽性診斷預測率，但它受到年齡、前列腺按摩、穿刺、感染、藥物等因素的影響，致使其診斷的敏感性、特異性不高，，不能充分滿足PCa早期診斷的需要，因此，PCa早期診斷急需要敏感特異的生物標記物。表觀遺傳學在腫瘤的發(fā)生發(fā)展中起到重要的作用，其中DNA異常甲基化是最重要的修飾方式，DNA甲基化不改變核苷酸的序列，而是通過改變?nèi)旧w結(jié)構(gòu)和組蛋白乙酰化作用的水平，間接導致基因轉(zhuǎn)錄抑制。異常甲基化是腫瘤發(fā)生的早期事件，所以DNA甲基化的檢測會成為惡性腫瘤早期診斷有價值的標記物。腫瘤是多基因變異積累的過程，因此，我們認為多種甲基化基因的聯(lián)合檢測,能彌補單基因檢測的缺陷。按照這樣的目的,我們篩查選用了SHOX2、GSTP1和RASSF1A三個基因進行甲基化特異性PCR聯(lián)合檢測，分析兩兩基因聯(lián)合檢測的最優(yōu)組合，提高PCa早期診斷的陽性率，挖掘在PCa早期診斷中的價值。 方法：本課題收集47例PCa石蠟組織與27例前列腺增生(BPH)石蠟組織，使用甲基化特異性PCR（MSP）方法分別對SHOX2、GSTP1和RASSF1A這3個的甲基化水平進行檢測。分析SHOX2、GSTP1和RASSF1A兩兩聯(lián)合檢測在PCa早期診斷中的意義。 結(jié)果：PCa組織中SHOX2、GSTP1和RASSF1A基因甲基化率分別為17.02%、51.06%、65.96%。BPH中分別為40.74%、3.70%、22.22%。PCa中GSTP1和RASSF1A基因甲基化陽性率均高于BPH中(P＜0.05)，而SHOX2基因甲基化陽性率在PCa中低于BPH(P＜0.05)。進行兩兩基因聯(lián)合比較（SHOX2+RASSF1A、SHOX2+GSTP1、GSTP1+RASSF1A）甲基化陽性率分別為70.21%、53.19%、87.23%。均高于單個基因的甲基化陽性率(P＜0.05)。 結(jié)論： 1.本研究顯示SHOX2在PCa的發(fā)生和發(fā)展中扮演原癌基因的角色。 2.GSTP1+RASSF1A甲基化聯(lián)合檢測敏感性較高，聯(lián)合檢測GSTP1+RASSF1A有望成為PCa早期診斷的生物標記物。
[Abstract]:Background: prostate cancer (PCA) is the most common malignant tumor in developed countries in Europe and America. The mortality of PCA is higher in China than in Europe and America. However, in recent years, the incidence of PCA in China is increasing obviously. It is the best treatment for the patients with early detection of focal PCA to undergo the radical operation of PCA. The goal of the ideal detection of PCA after recovery is to be able to diagnose the disease clearly at the early stage. Therefore, looking for early tumor markers of PCA has become an urgent problem for urologists. At present, serum prostate specific antigen (PSA), as a single detection index of PCA, is affected by age, prostate massage, puncture, infection, drug and so on, although it has a high predictive rate of positive diagnosis of PCA. As a result, the sensitivity and specificity of the diagnosis are not high, which can not fully meet the need of early diagnosis of PCA. Therefore, the early diagnosis of PCA needs sensitive and specific biomarkers. Epigenetics plays an important role in tumorigenesis and development. DNA methylation is the most important modification method. DNA methylation does not change the sequence of nucleotides, but by changing the chromosome structure and the level of histone acetylation. Indirect gene transcription inhibition. Abnormal methylation is an early event in tumorigenesis, so the detection of DNA methylation may be a valuable marker for the early diagnosis of malignant tumors. Tumor is a process of polygenic variation accumulation. Therefore, we think that the combined detection of multiple methylated genes can make up for the defects of single gene detection. In order to improve the positive rate of early diagnosis of PCA, we selected three genes of SHOX2GSTP1 and RASSF1A for methylation specific PCR, analyzed the optimal combination of them, and excavated their value in the early diagnosis of PCA. Methods: the methylation levels of SHOX2GSTP1 and RASSF1A were detected by methylation specific PCR (MSP) in 47 paraffin tissues of PCA and 27 paraffin tissues of benign prostatic hyperplasia (BPH). To analyze the significance of combined detection of SHOX2, GSTP1 and RASSF1A in the early diagnosis of PCA. Results the methylation rates of SHOX2GSTP1 and RASSF1A were 17.02and 51.065.96. the methylation rates of SHOX2GSTP1 and RASSF1A in BPH were 40.743.703.702.22.PCa, respectively (P < 0.05), but the positive rate of SHOX2 gene methylation in PCA was lower than that in BPH (P < 0.05). The methylation rate of SHOX2 gene in PCa was lower than that in BPH (P < 0.05), but the methylation rate of SHOX2 gene in PCa was lower than that in BPH (P < 0.05). The methylation positive rates of SHOX2 RASSF1AnSHOX2 GSTP1 RASSF1A were 70.21 and 53.19 respectively. The positive rate of methylation was higher than that of single gene (P < 0.05). Conclusion: 1. This study shows that SHOX2 plays the role of proto-oncogene in the genesis and development of PCA. 2. The combined detection of GSTP1 RASSF1A methylation is highly sensitive, and the combined detection of GSTP1 RASSF1A may be a biomarker for early diagnosis of PCA.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R737.25

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