EGFR基因突变与肺腺癌组织中EGFR、TTF-1表达、血清CEA水平的相关性研究

发布时间：2018-04-23 03:10

本文选题：肺腺癌 + 表皮生长因子受体　；参考：《青海大学》2017年硕士论文

【摘要】：背景与目的:肺癌一直是个困扰全世界的重大公共卫生难题,因肺癌致死的人数已经跃居恶性肿瘤的首位,严重威胁着人类健康。近二十年来肺癌中腺癌的构成比持续上升,有研究指出,全世界范围内肺腺癌的发病率已赶超鳞癌等其他肺癌病理类型,逐步成为最常见的病理类型。随着治疗方案的不断改进,近年来分子靶向药物发展最为迅猛,其中最为典型和成功的当属于EGFR酪氨酸激酶抑制剂(TKI)在晚期非小细胞病人中的治疗,尤其在合并EGFR突变的非小细胞肺癌病人中EGFR-TKI显示出了其巨大的应用潜力。而EGFR基因在肺腺癌组织中的突变率明显高于其他病理类型的肺癌,所以针对EGFR信号通路的分子靶向治疗已然成为晚期肺腺癌病人的重要治疗手段。然而,EGFR基因突变检测对肿瘤组织的获取、检测技术对操作员和实验室要求苛刻,我国范围内开展基因突变检测地区有限,且检测的费用高,在多数不发达地区或发达地区的基层医院的临床中很难完善。本研究旨在探索在肺腺癌患者中EGFR基因突变情况与其肿瘤中EGFR、TTF-1表达水平及血清CEA水平的相关性,以临床上易于获得的检测结果,预测腺癌病人EGFR基因是否存在突变,指导其应用EGFR-TKI治疗,制定更加合理的个体化诊疗方案。方法:搜集50例明确诊断为肺腺癌患者的新鲜病理组织,统计其各病人的基本临床特点,采用探针扩增阻滞突变系统(ARMS法)检查EGFR基因是否突变,同时应用免疫组织化学法测出病理组织细胞中EGFR和TTF-1的表达水平,并收集患者治疗前血清CEA水平。应用卡方检验及单因素、多因素的logistics回归等统计方法处理所得数据。结果:在全部50例样本资料之中,EGFR基因发生突变的阳性率为58%,EGFR表达阳性率为66%,TTF-1表达阳性率为84%,血清CEA异常增高率为40%。EGFR表达阳性患者中EGFR基因发生突变的共24例(73%),TTF-1表达阳性患者的EGFR基因发生突变的共26例(62%),治疗前血清CEA高值组的EGFR基因发生突变的共15例(75%)。经过卡法检验提示:EGFR基因是否存在突变与肺腺癌病人的性别、年龄、既往是否抽烟、肺癌不同的分期等各临床特点均无明确的关联性,无统计学意义上的差异(各P值全部0.05)。经过多因素logistics回归分析,肺腺癌组织中的EGFR阳性表达和治疗前血清CEA异常增高分别为EGFR发生突变的独立的危险因素,差异有统计学意义(OR=5.754,P=0.039;OR=5.344,P=0.040);而癌细胞中TTF-1表达与否不是EGFR是否发生突变的独立危险因素(OR=4.838,P=0.179)。结论:TTF-1是否表达与EGFR的基因是否突变无明显的相关性;治疗前CEA高值和EGFR阳性表达均是肺腺癌病人EGFR基因发生突变的独立危险因子。EGFR的表达程度与治疗前CEA数值在一定程度上可用来推测肺腺癌病人EGFR基因发生突变的概率,可以成为是否使用EGFR-TKI治疗的间接的客观指标。
[Abstract]:Background & objective: lung cancer has been a major public health problem in the world. The number of lung cancer deaths has leapt to the top of malignant tumors, which is a serious threat to human health. The proportion of adenocarcinoma in lung cancer has been increasing in the past two decades. It is pointed out that the incidence of lung adenocarcinoma has surpassed that of squamous cell carcinoma and has gradually become the most common pathological type of lung cancer. With the continuous improvement of therapeutic protocols, molecular targeted drugs have developed most rapidly in recent years, among which the most typical and successful treatment is EGFR tyrosine kinase inhibitor (TKI) in advanced non-small cell patients. Especially in patients with non-small cell lung cancer (NSCLC) with EGFR mutation, EGFR-TKI shows great potential for application. The mutation rate of EGFR gene in lung adenocarcinoma tissues is significantly higher than that in other types of lung cancer, so molecular targeting therapy for EGFR signaling pathway has become an important treatment for advanced lung adenocarcinoma patients. However, the detection of EGFR gene mutation is very demanding to the operators and laboratories. The detection of EGFR gene mutation is limited in China, and the cost of detection is high. It is difficult to improve the clinical practice of primary hospitals in most underdeveloped areas or developed areas. The purpose of this study was to investigate the correlation between EGFR gene mutation and the expression of EGFR TTF-1 and serum CEA levels in lung adenocarcinoma patients, and to predict whether there was mutation in EGFR gene in patients with adenocarcinoma. To guide the application of EGFR-TKI therapy, to formulate more rational individual diagnosis and treatment plan. Methods: the fresh pathological tissues of 50 patients with lung adenocarcinoma were collected, and the basic clinical characteristics of each patient were analyzed. The mutation of EGFR gene was detected by probe amplification block mutation system (ARMS). The expression levels of EGFR and TTF-1 in pathological tissues were detected by immunohistochemical method, and the serum CEA levels were collected before treatment. Chi-square test, single factor and multivariate logistics regression were used to process the data. Results: in all 50 samples, the positive rate of EGFR gene mutation was 58 and the positive rate of EGFR gene was 660.The positive rate of TTF-1 expression was 84. The abnormal increase rate of serum CEA was the mutation of EGFR gene in 24 patients with positive 40%.EGFR expression. There were 26 cases of EGFR gene mutation in positive patients and 15 cases of EGFR gene mutation in high value group of serum CEA before treatment. The results of card test showed that there was no significant correlation between the mutation of the 1% EGFR gene and the sex, age, smoking history, different stages of lung cancer, and there was no statistical difference (all P values were 0. 05%, P = 0. 05%, P = 0. 05%, P < 0. 05%, P = 0. 05). By multivariate logistics regression analysis, the positive expression of EGFR in lung adenocarcinoma tissues and the abnormal increase of serum CEA before treatment were independent risk factors for EGFR mutation, respectively. The difference was statistically significant (P < 0.01), and the expression of TTF-1 in cancer cells was not an independent risk factor for EGFR mutation. Conclusion there is no significant correlation between the expression of TTF-1 and the mutation of EGFR gene. The high value of CEA and the positive expression of EGFR before treatment are independent risk factors of EGFR gene mutation in lung adenocarcinoma patients. The CEA values before treatment can be used to predict the probability of EGFR gene mutation in lung adenocarcinoma patients. It can be an indirect objective indicator of whether or not to use EGFR-TKI therapy.
【学位授予单位】：青海大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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