ADH1和ALDH2基因在男性肝癌患者中的异常表达及其临床意义

发布时间：2018-02-02 01:11

本文关键词： ADH ALDH 生存时间原发性肝癌　出处：《郑州大学》2016年硕士论文　论文类型：学位论文

【摘要】：乙醇俗称酒精,在肝脏中的主要代谢过程包括三个步骤：首先乙醇被乙醇脱氢酶(ADH)氧化为乙醛,然后乙醛被乙醛脱氢酶(ALDH)氧化为乙酸,最后乙酸分解为二氧化碳和水等物质。酒精代谢与肝癌的发生发展有关。乙醇在肝脏中主要被ADH酶和ALDH酶代谢,这两种酶类分别是由ADH和ALDH基因编码。这两类基因的改变与多种恶性肿瘤相关,其中也包括原发性肝癌。然而,这两类基因对肝癌患者的预后价值并不十分清楚。目的检测ADH和ALDH基因在男性原发性肝癌患者中的表达水平,并分析其表达水平与患者术后预后的关联。方法1.采集了85例男性肝癌患者的癌组织及配对的癌旁组织,并收集其术前临床资料,随访其术后状况。2.运用实时荧光定量PCR方法检测了85例男性肝癌患者的癌组织与癌旁组织中ADH1和ALDH2基因的表达情况。3.统计分析：运用Wilcoxon方法分析比较ADH1和ALDH2的mRNA表达水平在肿瘤组织和邻近的癌旁组织中的差异。运用Mann-Whitney方法分析比较ADH1和ALDH2的mRNA表达水平在饮酒与非饮酒患者间的差异。各基因表达水平之间的相关性使用Spearman等级相关分析。不同分组的总体生存时间曲线和无复发生存时间曲线使用Kaplan-Meier方法绘制。运用Log-rank方法分析了患者的临床资料及基因的表达与患者术后生存时间、无复发生存时间的关联。运用多因素Cox回归分析患者术后的生存与复发相关的可能的独立预后风险因素。结果1.与癌旁组织相比,癌组织中ADH1和ALDH2基因的表达均较低(P0.001),且ADH1和ALDH2基因的表达呈现正相关。2. Kaplan-Meier分析显示患者的ADH1B和ALDH2基因在癌组织和癌旁组织的表达水平的比值较低的情况下,术后无复发时间较短(P=0.002,P=0.007),而且ADH1B基因在癌组织和癌旁组织的表达水平的比值较低时与较差的术后生存时间有关(P=0.017)。同时,不管是癌组织还是癌旁组织中患者的ADH1A(P=0.026,P=0.003)和ALDH2 (P=0.044, P=0.010)的表达水平较低时,术后总体生存时间都较短。多因素Cox回归分析结果显示, ADH1B基因在癌与癌旁组织中表达水平的比值是肝癌患者术后无复发时间的独立预后指标,同时ADH1A基因在癌旁组织的表达水平是肝癌患者术后生存时间的独立预后指标。结论1.男性肝癌患者中的癌组织中ADH1和ALDH2的表达水平均显著低于癌旁组织,且ADH1和ALDH2基因表达呈现相关性。2. ADH1B基因在癌与癌旁中表达水平的比值较低时,男性肝癌患者的术后无复发时间较短,同时癌旁组织中ADH1A表达水平较低时,男性肝癌患者的术后生存时间较短。
[Abstract]:Ethanol, commonly known as alcohol, is mainly metabolized in the liver by three steps: first, ethanol is oxidized to acetaldehyde by alcohol dehydrogenase (ADH), and then acetaldehyde is oxidized to acetic acid by acetaldehyde dehydrogenase (ALDH). Finally, acetic acid is decomposed into carbon dioxide and water. Alcohol metabolism is related to the occurrence and development of liver cancer. Ethanol is mainly metabolized by ADH enzyme and ALDH enzyme in liver. The two enzymes are encoded by the ADH and ALDH genes, respectively. The changes in these two genes are associated with a variety of malignant tumors, including primary liver cancer. The prognostic value of these two genes is not very clear. Objective to detect the expression of ADH and ALDH genes in male patients with primary liver cancer. The relationship between the expression level and postoperative prognosis was analyzed. 1. The cancer tissues and matched adjacent tissues of 85 male patients with liver cancer were collected and the preoperative clinical data were collected. 2. The expression of ADH1 and ALDH2 genes in 85 male patients with hepatocellular carcinoma and adjacent tissues were detected by real-time fluorescence quantitative PCR. 3. Statistical analysis:. Wilcoxon method was used to analyze and compare the mRNA expression levels between ADH1 and ALDH2 in tumor tissues and adjacent paracancerous tissues. Mann-Whitney method was used to analyze and compare the expression levels of mRNA between tumor tissues and adjacent paracancerous tissues. The mRNA expression levels of ADH1 and ALDH2 were analyzed and compared between drinking and non-drinking patients. The correlation between the gene expression levels using Spearman grade correlation analysis. Different groups. Total survival time curve and relapse free survival time curve were plotted by Kaplan-Meier method. Log-rank method was used to analyze the clinical data, gene expression and patient operation. After survival time. Multivariate Cox regression analysis was used to analyze the possible independent prognostic risk factors associated with postoperative survival and recurrence. Results 1.Compared with paracancerous tissues. The expression of ADH1 and ALDH2 genes were both low in cancer tissues (P0.001). The expression of ADH1 and ALDH2 gene was positively correlated with that of ALDH2 gene. Kaplan-Meier analysis showed that the ratio of ADH1B and ALDH2 gene expression in cancer tissues and adjacent tissues was low. The time of no recurrence after operation was shorter than that of P0. 002 and P0. 007 (P < 0. 007). Moreover, the low expression ratio of ADH1B gene in cancer tissues and adjacent tissues was related to the poor survival time after operation. At the same time, the ratio of ADH1B gene expression in cancer tissues and adjacent tissues was related to the poor survival time. In both cancerous and paracarcinomatous tissues, the ADH1 A1A1a (0.026) P0. 003 and ALDH2 P0. 044 (P < 0. 044) were found in the patients. Multivariate Cox regression analysis showed that the overall survival time was shorter when the expression level of Pn0. 010) was lower. The ratio of ADH1B gene expression in cancer to paracancerous tissues is an independent prognostic indicator of no recurrence time after operation in patients with liver cancer. At the same time, the expression of ADH1A gene in adjacent tissues is an independent prognostic index of postoperative survival time of HCC patients. Conclusion 1. The expression of ADH1 and ALDH2 in the cancer tissues of male patients with hepatocellular carcinoma are both positive. 2. Significantly lower than paracancerous tissue. The expression of ADH1 and ALDH2 was correlated with the expression of ADH1B gene. When the ratio of ADH1B gene expression in cancer to adjacent tumor was lower, the time of no recurrence was shorter in male patients with liver cancer. At the same time, the survival time of male patients with liver cancer was shorter when the expression of ADH1A was lower in paracancerous tissues.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R735.7

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