【摘要】：國際癌癥研究機構(the International Agency for Research on Cancer,IARC)研究數(shù)據(jù)顯示,2012年全球七分之一的死亡由癌癥造成,隨著癌癥發(fā)病率和死亡率的不斷增加,2010至今,癌癥已經(jīng)成為我國死亡的主要原因。2012年全球肝癌新發(fā)病例達782500例,死亡病例達745500例,且近一半出現(xiàn)在中國。同年,全球肺癌新發(fā)病例達1800000例。2015研究數(shù)據(jù)報道肺癌是中國最常見癌癥類型,也是主要的癌癥致死類型。其中,肝細胞肝癌(hepatocellular carcinoma, HCC)占原發(fā)性肝癌的70%-90%,非小細胞肺癌(non-small cell lung carcinoma, NSCLC)占肺癌的80%-85%。研究顯示早期發(fā)現(xiàn)并確診HCC、NSCLC等惡性腫瘤,并對患者進行有效治療將會明顯提高患者預后、延長患者生存期,然而由于缺乏有效的早期診斷方式,導致80%以上HCC患者、65%以上NSCLC患者在確診時已為中晚期,錯過了有效的治療時機,因此5年生存率低,給患者個人造成健康及生命損害的同時也給家庭、社會帶來嚴重的經(jīng)濟負擔。本研究旨在通過Luminex技術建立高效、準確的HCC、NSCLC等其他惡性腫瘤診斷方法。第一部分肝癌研究中,我們通過文獻篩選后合成9指標Luminex試劑盒,在共計1200例的不同疾病及健康對照血清樣本中進行檢測并進行單獨及聯(lián)合指標分析。研究發(fā)現(xiàn)癌胚抗原相關細胞粘附分子1(carcinoembryonic antigen1, CEACAM1)在HCC診斷中具有較高的靈敏度和特異性,可作為HCC獨立的血清學診斷標志物。將此新指標與臨床通用HCC篩查指標甲胎蛋白(alpha fetal protein,AFP)以及目前研究報道中對HCC具有有效檢測診斷作用的高爾基蛋白73(golgi protein73, GP73)聯(lián)合,可以進一步提高對HCC的診斷效力,特別是對早期HCC。與此同時,CEACAM1與GP73的聯(lián)合,對AFP(-)的HCC有很好的補充檢測作用。結合臨床資料分析顯示,CEACAM1與AFP、GP73的血清表達量對HCC的疾病進程及肝損傷程度都有有效的指示作用。另外,我們還研究發(fā)現(xiàn)GP73與其他指標組合可作為癌癥篩查的潛在通用指標,如與DKK1聯(lián)合對結直腸癌(colorectal carcinoma, CC)、食管癌(esophageal carcinoma, EC)有很好的診斷檢測效力,與HGF聯(lián)合對胃癌(gastric carcinoma, GC)有較好的診斷檢測效力。第二部分肺癌研究中,我們以多種腫瘤相關自身抗體為研究方向,對93例血清樣NSCLC及健康對照樣本進行23種腫瘤相關自身抗體的同步檢測,并進行單獨及聯(lián)合指標分析。研究發(fā)現(xiàn)腫瘤-睪丸抗原(cancer testis antigen 1B, NY-ESO-1)、腫瘤蛋白p53 (tumor protein p53, p53)、細胞周期素依賴性蛋白激酶2(cyclin-dependent kinase 2, CDK2)、膜聯(lián)蛋白A2(annexinA2)、胰島素樣生長因子2 mRNA結合蛋白1 (insulin-like growth factor 2 mRNA binding proteinl, IMP1)、泛素1(ubiquilin1)以及磷酸甘油酸變位酶(phosphoglycerate mutase1, PGAM1)共7種自身抗體在NSCLC的診斷中均有一定意義,當7項指標聯(lián)合檢測時,可進一步有效提高對NSCLC的診斷準確性。綜上所述,本研究利用Luminex技術建立了高效、準確的HCC、NSCLC等惡性腫瘤的診斷方法,為實現(xiàn)疾病早期診斷、治療和療效監(jiān)測以及多種其他癌癥的篩查提供參考。
[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.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R730.4

【相似文獻】

相關期刊論文 前1條

1 趙培革;魯?shù)聅，

本文編號：2212551