血清Talin-1在肝细胞癌诊断中的作用

发布时间：2018-08-10 21:08

【摘要】：研究背景原发性肝癌(Primary Liver Cancer,PLC)简称肝癌,是世界范围内发病率位居第五的恶性肿瘤,每年新增病例超过100万人,严重危害人类生命健康[1]。当下,肝癌在全球的发病率呈上升趋势,在我国肝癌年发病率居第4位,肿瘤死亡率居第2位。《全球癌症报告2014》显示,肝癌的新增病例、死亡人数均居于世界第一位,HCC的死亡率占全球的51%。病毒性肝炎、酒精、肝硬化、黄曲霉毒素、饮用水污染、遗传因素、亚硝胺类等是可能的致病原因。在我国,慢性病毒性肝炎是肝癌诸多致病因素中最主要的病因,流行病学调查发现约1/3患者有慢性肝炎病史,85%~90%的肝癌与乙肝病毒相关,5%-8%的患者抗HCV抗体呈现阳性。HCC起病隐匿,早期缺乏典型症状,临床症状明显者大多已进入中晚期,而且其恶性程度高,容易复发及转移,手术切除率低,复发率高,预后差,而且早期诊断较困难,延误了最佳治疗时期。因此,早期发现、早期诊断是提高治疗效果的前提。肝癌的诊断主要根据血清学检测、影像学检查及肝穿刺,而血清学检测主要是检测甲胎蛋白(alpha fetoprotein,AFP),AFP是目前用于诊断HCC最实在且可行的血清学标志物。然而,AFP较低的敏感性和特异性限制了其作用,这就迫切要求我们去寻找能够诊断HCC的新的生物学标志物。踝蛋白(Talin)是一类大分子细胞骨架蛋白,是粘附细胞黏着斑中心的一个重要组成部分,能与多种细胞粘附分子相结合。踝蛋白是第一个被证实的能与整合素相结合的细胞骨架蛋白,参与调节细胞粘附、转移及扩散,并能促进肿瘤的发生发展。近年来相关研究表明Talin-1在肿瘤的转移和和浸润过程中发挥重要作用。Talin-1是踝蛋白家族的一个重要组成成分,在肿瘤的粘附和迁移中起着至关重要的作用。Talin-1主要在前列腺、肾、胃、肝、脾、肺及血管平滑肌等组织中表达,研究表明其过度表达与前列腺癌的黏附、转移和浸润密切相关。近年来相关研究表明Talin-1对于HCC的发展来说是一个新的分子学标志物。然而,Talin-1作为血清学标志物对于HCC的诊断及预后评估尚缺乏相关的研究。目的研究原发性肝细胞癌患者血清中的踝蛋白1(Talin-1)的浓度,将其与传统的生物学标志物甲胎蛋白(alpha-fetoprotein,AFP,)相比,探讨其在肝细胞癌诊断中的作用。方法采用酶联免疫吸附试验(Enzyme Linked Immunosorbent Assay,ELISA)分别检测120例血清样本中的Talin-1,分组情况为肝细胞癌血清40例、肝硬化(Liver Cirrhosis,LC)血清40例、正常对照组血清40例。分类变量及连续变量间的差异比较采用卡方检验、t检验或单因素方差分析;三个样本组血清Talin-1水平与其他变量间的比较采用非参数检验K-W或M-W检验,相关性采用Spearman等级相关分析;ROC受试者诊断特征曲线(Operating Characterristic Curve)分析Talin-1与AFP在HCC诊断中的敏感性、特异性。检验水准α=0.05,P0.05表示差异具有统计学意义。结果用ROC曲线创建一个Talin-1与AFP相比较的诊断预测模型。HCC组中Talin-1的表达水平高于LC组、健康对照组(P=0.0000.05)。在诊断肝细胞癌时,Talin-1的敏感性和特异性均明显高于AFP的敏感性、特异性。结论Talin-1在HCC的诊断中可能是一个潜在的生物学标志物,相对于传统的生物学标志物AFP而言,Talin-1具有更高的敏感性和特异性。
[Abstract]:Background Primary Liver Cancer (PLC) is the fifth most common malignant tumor in the world, with an annual increase of more than 1 million cases, seriously endangering human life and health. According to the Global Cancer Report 2014, the number of new cases of liver cancer is the highest in the world, with the mortality rate of HCC accounting for 51%. Viral hepatitis, alcohol, cirrhosis, aflatoxin, drinking water pollution, genetic factors and nitrosamines are the possible causes of liver cancer. Chronic viral hepatitis is one of the most common causes of liver cancer in China. Epidemiological investigation showed that about one third of the patients had a history of chronic hepatitis, 85% - 90% of the liver cancer was associated with hepatitis B virus, 5% - 8% of the patients showed positive anti-HCV antibodies. HCC onset was hidden, early lack of typical symptoms, most of the patients with obvious clinical symptoms have entered the advanced stage, and its malignancy is high, easy to recur and metastasis, hand. Therefore, early detection and early diagnosis are the prerequisites for improving the therapeutic effect. The diagnosis of liver cancer is mainly based on serological detection, imaging examination and liver puncture, while serological detection is mainly based on alpha fetoprotein (AFP), A. FP is the most reliable and feasible serological marker for the diagnosis of HCC at present. However, the low sensitivity and specificity of AFP limit its role, which urgently requires us to find new biomarkers for the diagnosis of HCC. Ankle protein is the first confirmed cytoskeletal protein that binds to integrin. It regulates cell adhesion, metastasis and diffusion, and promotes tumor development. Recent studies have shown that Talin-1 plays an important role in tumor metastasis and invasion. Talin-1 is an important component of the ankle protein family and plays an important role in tumor adhesion and migration. Talin-1 is mainly expressed in prostate, kidney, stomach, liver, spleen, lung and vascular smooth muscle. Studies have shown that its overexpression is closely related to prostate cancer adhesion, metastasis and invasion. Ming Talin-1 is a new molecular marker for the development of HCC. However, as a serological marker, there is no relevant study on the diagnosis and prognosis of HCC. Methods Enzyme Linked Immunosorbent Assay (ELISA) was used to detect Talin-1 in 120 serum samples, which were divided into 40 serum samples of hepatocellular carcinoma, 40 serum samples of liver cirrhosis (LC) and 40 serum samples of normal control group. Chi-square test, t-test or one-way ANOVA were used to compare the differences between class variables and continuous variables; non-parametric K-W or M-W test was used to compare the levels of Talin-1 between three sample groups and other variables; Spearman grade correlation analysis was used to analyze the correlation; Operating Characteristic Curve was used to score ROC subjects. The sensitivity and specificity of Talin-1 and AFP in the diagnosis of HCC were analyzed. Test level alpha = 0.05, P 0.05 showed significant difference. Results ROC curve was used to create a diagnostic prediction model of Talin-1 compared with AFP. The expression level of Talin-1 in HCC group was higher than that in LC group and healthy control group (P = 0.0000.05). Conclusion Talin-1 may be a potential biomarker in the diagnosis of HCC. Compared with traditional biomarker AFP, Talin-1 has higher sensitivity and specificity.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.7

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