SHOX2、GSTP1和RASSF1A甲基化联合检测在前列腺癌诊断中的研究

发布时间：2018-07-05 00:21

本文选题：SHOX2 + GSTP1　；参考：《山西医科大学》2014年硕士论文

【摘要】：背景：前列腺癌（PCa）是欧美发达国家男性发病率最高的恶性肿瘤，死亡率也较高。PCa在我国的发病率较欧美低，但近年来，我国PCa的发病率呈现明显上升趋势。对于早期发现的局灶性PCa的患者进行PCa根治手术是最好的治疗手段,愈后理想。PCa检测的目标就在于能够在疾病的早期明确诊断。因此，寻找PCa早期肿瘤标志物成为泌尿外科临床医师急需解决的问题。目前，血清前列腺特异性抗原（PSA）作为PCa的单一检测指标，虽然具有较高的PCa阳性诊断预测率，但它受到年龄、前列腺按摩、穿刺、感染、药物等因素的影响，致使其诊断的敏感性、特异性不高，，不能充分满足PCa早期诊断的需要，因此，PCa早期诊断急需要敏感特异的生物标记物。表观遗传学在肿瘤的发生发展中起到重要的作用，其中DNA异常甲基化是最重要的修饰方式，DNA甲基化不改变核苷酸的序列，而是通过改变染色体结构和组蛋白乙酰化作用的水平，间接导致基因转录抑制。异常甲基化是肿瘤发生的早期事件，所以DNA甲基化的检测会成为恶性肿瘤早期诊断有价值的标记物。肿瘤是多基因变异积累的过程，因此，我们认为多种甲基化基因的联合检测,能弥补单基因检测的缺陷。按照这样的目的,我们筛查选用了SHOX2、GSTP1和RASSF1A三个基因进行甲基化特异性PCR联合检测，分析两两基因联合检测的最优组合，提高PCa早期诊断的阳性率，挖掘在PCa早期诊断中的价值。方法：本课题收集47例PCa石蜡组织与27例前列腺增生(BPH)石蜡组织，使用甲基化特异性PCR（MSP）方法分别对SHOX2、GSTP1和RASSF1A这3个的甲基化水平进行检测。分析SHOX2、GSTP1和RASSF1A两两联合检测在PCa早期诊断中的意义。结果：PCa组织中SHOX2、GSTP1和RASSF1A基因甲基化率分别为17.02%、51.06%、65.96%。BPH中分别为40.74%、3.70%、22.22%。PCa中GSTP1和RASSF1A基因甲基化阳性率均高于BPH中(P＜0.05)，而SHOX2基因甲基化阳性率在PCa中低于BPH(P＜0.05)。进行两两基因联合比较（SHOX2+RASSF1A、SHOX2+GSTP1、GSTP1+RASSF1A）甲基化阳性率分别为70.21%、53.19%、87.23%。均高于单个基因的甲基化阳性率(P＜0.05)。结论： 1.本研究显示SHOX2在PCa的发生和发展中扮演原癌基因的角色。 2.GSTP1+RASSF1A甲基化联合检测敏感性较高，联合检测GSTP1+RASSF1A有望成为PCa早期诊断的生物标记物。
[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.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.25

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