CYLD、GOLPH3和NF-κB mRNA在肝细胞癌患者外周血中表达水平及其诊断价值

发布时间：2018-03-28 09:06

  本文选题：肝细胞癌　切入点：圆柱瘤基因　出处：《青岛大学》2017年硕士论文

【摘要】：【目的】分析圆柱瘤基因(cylindromatosis,CYLD)、高尔基体3(Golgi phosphoprotein3,GOLPH3)、核转录因子kappa B1(NF-κB1)和Rel A mRNA在肝细胞癌(hepatocellular carcinoma,HCC)、肝硬化、慢性肝炎患者和健康对照组外周血中的表达水平及其与HCC患者临床特征的关系;利用受式者工作特性曲线(ROC)分析四种癌基因mRNA表达水平对HCC早期诊断的价值。【方法】以2016年1月至2016年10月青岛大学医学院附属医院就诊HCC患者90例、肝硬化患者41例、慢性肝炎患者46例以及健康体检者80例作为研究对象。利用RT-PCR检测四组研究对象外周血CYLD、GOLPH3、NF-κB1和Rel A mRNA的相对表达水平;全自动生化仪检测血清总胆红素(serum total bilirubin,STB)、谷草转氨酶(aspartate aminotransferase,AST)和谷丙转氨酶(alanine aminotransferase,ALT)。受试者工作特征曲线(receiver operating characteristic,ROC)分析AFP、CYLD、GOLPH3、NF-κB1和Rel A mRNA对肝细胞癌的早期诊断价值。【结果】HCC组外周血中CYLD mRNA的相对表达量显著低于其它三组,其中肝硬化组明显高于正常组和肝炎组,GOLPH3、NF-ΚB1和Rel A mRNA在HCC中的表达显著高于其它三组。CYLD mRNA相对表达量在肿瘤大于等于5cm和高转氨酶水平的患者中明显降低(P0.05);GOLPH3 mRNA相对表达量在转移、Ⅲ/Ⅳ期和高Ki67指数患者中呈现高表达(P0.05);NF-ΚB1和Rel A mRNA在Ⅲ/Ⅳ期的患者血液中高表达(P0.05),Rel A mRNA在门静脉癌栓阳性和高Ki67指数的患者血液中高表达(P0.05)。五个指标(血清AFP和CYLD、GOLPH3、NF-κB1以及Rel A mRNA表达水平)的单独诊断价值分析显示,AFP和CYLD mRNA ROC曲线下面积分别为0.828和0.847;而GOLPH3、NF-κB1和Rel A基因mRNA表达对HCC的诊断价值较低,曲线下面积分别为0.677、0.658和0.623。联合检测血清AFP水平和CYLD基因mRNA表达,其灵敏度、特异度和曲线下面积分别是0.889、0.762和0.897,显著高于AFP和CYLD的单独诊断价值(P0.05)。在AFP阴性者中,CYLD仍然对肝癌有一定的诊断价值,曲线下面积是0.821,可以在一定程度上弥补AFP敏感性的不足。【结论】1.HCC组CYLD mRNA相对表达量低于肝硬化组、肝炎组和正常组,其中CYLD mRNA相对表达量在肝硬化患者中明显高于正常人和肝炎患者GOLPH3、NF-ΚB1和Rel A在HCC患者外周中的相对表达明显高于其它三组。提示CYLD、GOLPH3、NF-ΚB1和Rel A与HCC密切相关。2.在肿瘤大于5cm、血清转氨酶水平较高的HCC患者中,CYLD mRNA的相对表达量降低;GOLPH3 mRNA的相对表达量在转移、Ⅲ/Ⅳ期和高Ki67增殖指数患者中升高;NF-ΚB1 mRNA的相对表达量在Ⅲ/Ⅳ期患者中升高;Rel A mRNA相对表达量在门静脉癌栓阳性、Ⅲ/Ⅳ期和高Ki67增殖指数患者中升高。CYLD、GOLPH3、NF-ΚB1和Rel AmRNA可能与肝癌的预后有关。3.CYLD对HCC的早期诊断有一定的准确性,AFP和CYLD的联合诊断价值显著高于AFP和CYLD单独诊断的准确性。在AFP阴性者中CYLD仍然具有一定的诊断价值,说明其在一定程度上可以弥补AFP敏感性低的不足。
[Abstract]:[objective] to analyze the expression levels of Cyd Cyd, Golgi body 3(Golgi phosphoprotein 3, nuclear transcription factor kappa B1 NF- 魏 B1 and Rel A mRNA in the peripheral blood of hepatocellular carcinoma (HCC), liver cirrhosis, chronic hepatitis and healthy controls and their relationship with the clinical characteristics of HCC patients. The value of mRNA expression of four kinds of oncogenes in the early diagnosis of HCC was analyzed by using the working characteristic curve of recipients. [methods] 90 patients with HCC and 41 patients with liver cirrhosis were admitted to the affiliated Hospital of Qingdao University Medical College from January 2016 to October 2016. 46 patients with chronic hepatitis and 80 healthy controls were used to detect the relative expression levels of CYLDG-GOLPH3NF- 魏 B1 and Rel A mRNA in peripheral blood by RT-PCR. Serum total bilirubin (STB), aspartate aminotransferase (AST), alanine aminotransferase (alt) and alanine aminotransferase (alt) were detected by automatic biochemical instrument. The diagnostic value of total LDLDPE NF- 魏 B1 and Rel A mRNA in patients with hepatocellular carcinoma was analyzed by receiver operating character roc. [results] in HCC group, the value of Rel A mRNA in early diagnosis of hepatocellular carcinoma was analyzed. The relative expression of CYLD mRNA in blood was significantly lower than that in the other three groups. The expression of Rel A mRNA and NF- KB1 in HCC in cirrhosis group was significantly higher than that in normal group and hepatitis group. The relative expression of CYLD mRNA in HCC was significantly higher than that in other three groups. The relative expression of CYLD mRNA in patients with tumor larger than 5cm and high transaminase level was significantly lower than that in normal group and hepatitis group. In patients with stage 鈪，

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