利用Luminex联合检测技术建立肝癌等恶性肿瘤高效、准确血清学诊断方法的研究
发布时间：2018-08-30 08:37
【摘要】：国际癌症研究机构(the International Agency for Research on Cancer,IARC)研究数据显示,2012年全球七分之一的死亡由癌症造成,随着癌症发病率和死亡率的不断增加,2010至今,癌症已经成为我国死亡的主要原因。2012年全球肝癌新发病例达782500例,死亡病例达745500例,且近一半出现在中国。同年,全球肺癌新发病例达1800000例。2015研究数据报道肺癌是中国最常见癌症类型,也是主要的癌症致死类型。其中,肝细胞肝癌(hepatocellular carcinoma, HCC)占原发性肝癌的70%-90%,非小细胞肺癌(non-small cell lung carcinoma, NSCLC)占肺癌的80%-85%。研究显示早期发现并确诊HCC、NSCLC等恶性肿瘤,并对患者进行有效治疗将会明显提高患者预后、延长患者生存期,然而由于缺乏有效的早期诊断方式,导致80%以上HCC患者、65%以上NSCLC患者在确诊时已为中晚期,错过了有效的治疗时机,因此5年生存率低,给患者个人造成健康及生命损害的同时也给家庭、社会带来严重的经济负担。本研究旨在通过Luminex技术建立高效、准确的HCC、NSCLC等其他恶性肿瘤诊断方法。第一部分肝癌研究中,我们通过文献筛选后合成9指标Luminex试剂盒,在共计1200例的不同疾病及健康对照血清样本中进行检测并进行单独及联合指标分析。研究发现癌胚抗原相关细胞粘附分子1(carcinoembryonic antigen1, CEACAM1)在HCC诊断中具有较高的灵敏度和特异性,可作为HCC独立的血清学诊断标志物。将此新指标与临床通用HCC筛查指标甲胎蛋白(alpha fetal protein,AFP)以及目前研究报道中对HCC具有有效检测诊断作用的高尔基蛋白73(golgi protein73, GP73)联合,可以进一步提高对HCC的诊断效力,特别是对早期HCC。与此同时,CEACAM1与GP73的联合,对AFP(-)的HCC有很好的补充检测作用。结合临床资料分析显示,CEACAM1与AFP、GP73的血清表达量对HCC的疾病进程及肝损伤程度都有有效的指示作用。另外,我们还研究发现GP73与其他指标组合可作为癌症筛查的潜在通用指标,如与DKK1联合对结直肠癌(colorectal carcinoma, CC)、食管癌(esophageal carcinoma, EC)有很好的诊断检测效力,与HGF联合对胃癌(gastric carcinoma, GC)有较好的诊断检测效力。第二部分肺癌研究中,我们以多种肿瘤相关自身抗体为研究方向,对93例血清样NSCLC及健康对照样本进行23种肿瘤相关自身抗体的同步检测,并进行单独及联合指标分析。研究发现肿瘤-睾丸抗原(cancer testis antigen 1B, NY-ESO-1)、肿瘤蛋白p53 (tumor protein p53, p53)、细胞周期素依赖性蛋白激酶2(cyclin-dependent kinase 2, CDK2)、膜联蛋白A2(annexinA2)、胰岛素样生长因子2 mRNA结合蛋白1 (insulin-like growth factor 2 mRNA binding proteinl, IMP1)、泛素1(ubiquilin1)以及磷酸甘油酸变位酶(phosphoglycerate mutase1, PGAM1)共7种自身抗体在NSCLC的诊断中均有一定意义,当7项指标联合检测时,可进一步有效提高对NSCLC的诊断准确性。综上所述,本研究利用Luminex技术建立了高效、准确的HCC、NSCLC等恶性肿瘤的诊断方法,为实现疾病早期诊断、治疗和疗效监测以及多种其他癌症的筛查提供参考。
[Abstract]:According to the International Agency for Research on Cancer (IARC), one-seventh of the world's deaths in 2012 were caused by cancer. With the increasing incidence and mortality of cancer, cancer has become the leading cause of death in China since 2010. In the same year, the number of new cases of lung cancer worldwide reached 180 000. According to the 2015 data, lung cancer is the most common type of cancer in China and the main type of cancer death. Hepatocellular carcinoma (HCC) accounts for 70-90% of primary liver cancer and non-small cell lung cancer (non-small cell lung cancer). Ll cell lung carcinoma (NSCLC) accounts for 80% - 85% of lung cancer. Studies have shown that early detection and diagnosis of HCC, NSCLC and other malignant tumors, and effective treatment of patients will significantly improve the prognosis and prolong the survival of patients. However, due to the lack of effective early diagnosis, more than 80% of HCC patients, 65% of NSCLC patients have been diagnosed at the time of diagnosis. This study aims to establish an efficient and accurate diagnostic method for HCC, NSCLC and other malignant tumors by Luminex technique. Part I: Hepatocellular carcinoma study, we Luminex reagent kit was synthesized by literature screening and tested in 1200 serum samples of different diseases and healthy controls.Carcinoembryonic antigen-associated cell adhesion molecule 1 (CEACAM1) was found to have high sensitivity and specificity in the diagnosis of HCC. It can be used as an independent serological diagnostic marker for HCC. Combining this new marker with a universal clinical HCC screening marker, alpha fetal protein (AFP), and Golgi protein 73 (GP73), which has been reported to be an effective diagnostic marker for HCC, can further improve the diagnostic efficacy of HCC, especially for early detection. At the same time, the combination of CEACAM1 and GP73 has a good complementary effect on HCC of AFP (-). Combined with clinical data analysis, the serum levels of CEACAM1, AFP and GP73 can effectively indicate the progression of HCC and the degree of liver injury. In addition, we also found that the combination of GP73 and other indicators can be used for cancer screening. Potential universal indicators, such as DKK1 combined with colorectal cancer (CC), esophageal cancer (EC) has a good diagnostic detection effect, and HGF combined with gastric cancer (GC) has a good diagnostic detection effect. In the second part of lung cancer research, we studied a variety of tumor-related autoantibodies. Direction: Synchronous detection of 23 tumor-associated autoantibodies was performed in 93 serum-like NSCLC and healthy control samples. Cancer testis antigen 1B (NY-ESO-1), tumor protein p53 (p53), cyclin-dependent protein kinase 2 (cyclin-dependent kinase) were detected. Seven autoantibodies including NT kinase 2, CDK2, annexin A2, insulin-like growth factor 2 mRNA binding protein 1 (IMP1), ubiquitin 1 (ubiquitin 1) and phosphoglycerate mutase 1 (PGAM1) have certain significance in the diagnosis of NSCLC. In summary, Luminex technique was used to establish a highly effective and accurate method for the diagnosis of HCC, NSCLC and other malignant tumors, which could provide a reference for early diagnosis, treatment and monitoring of curative effect and screening of many other cancers.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R730.4
[Abstract]:According to the International Agency for Research on Cancer (IARC), one-seventh of the world's deaths in 2012 were caused by cancer. With the increasing incidence and mortality of cancer, cancer has become the leading cause of death in China since 2010. In the same year, the number of new cases of lung cancer worldwide reached 180 000. According to the 2015 data, lung cancer is the most common type of cancer in China and the main type of cancer death. Hepatocellular carcinoma (HCC) accounts for 70-90% of primary liver cancer and non-small cell lung cancer (non-small cell lung cancer). Ll cell lung carcinoma (NSCLC) accounts for 80% - 85% of lung cancer. Studies have shown that early detection and diagnosis of HCC, NSCLC and other malignant tumors, and effective treatment of patients will significantly improve the prognosis and prolong the survival of patients. However, due to the lack of effective early diagnosis, more than 80% of HCC patients, 65% of NSCLC patients have been diagnosed at the time of diagnosis. This study aims to establish an efficient and accurate diagnostic method for HCC, NSCLC and other malignant tumors by Luminex technique. Part I: Hepatocellular carcinoma study, we Luminex reagent kit was synthesized by literature screening and tested in 1200 serum samples of different diseases and healthy controls.Carcinoembryonic antigen-associated cell adhesion molecule 1 (CEACAM1) was found to have high sensitivity and specificity in the diagnosis of HCC. It can be used as an independent serological diagnostic marker for HCC. Combining this new marker with a universal clinical HCC screening marker, alpha fetal protein (AFP), and Golgi protein 73 (GP73), which has been reported to be an effective diagnostic marker for HCC, can further improve the diagnostic efficacy of HCC, especially for early detection. At the same time, the combination of CEACAM1 and GP73 has a good complementary effect on HCC of AFP (-). Combined with clinical data analysis, the serum levels of CEACAM1, AFP and GP73 can effectively indicate the progression of HCC and the degree of liver injury. In addition, we also found that the combination of GP73 and other indicators can be used for cancer screening. Potential universal indicators, such as DKK1 combined with colorectal cancer (CC), esophageal cancer (EC) has a good diagnostic detection effect, and HGF combined with gastric cancer (GC) has a good diagnostic detection effect. In the second part of lung cancer research, we studied a variety of tumor-related autoantibodies. Direction: Synchronous detection of 23 tumor-associated autoantibodies was performed in 93 serum-like NSCLC and healthy control samples. Cancer testis antigen 1B (NY-ESO-1), tumor protein p53 (p53), cyclin-dependent protein kinase 2 (cyclin-dependent kinase) were detected. Seven autoantibodies including NT kinase 2, CDK2, annexin A2, insulin-like growth factor 2 mRNA binding protein 1 (IMP1), ubiquitin 1 (ubiquitin 1) and phosphoglycerate mutase 1 (PGAM1) have certain significance in the diagnosis of NSCLC. In summary, Luminex technique was used to establish a highly effective and accurate method for the diagnosis of HCC, NSCLC and other malignant tumors, which could provide a reference for early diagnosis, treatment and monitoring of curative effect and screening of many other cancers.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R730.4
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1 赵培革;鲁德s，
本文编号：2212551
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