黑色素瘤抗原-As在肺癌患者肿瘤组织及外周血中的表达及其临床意义

发布时间：2018-06-11 12:48

本文选题：肺癌 + 黑色素瘤抗原-As　；参考：《河北医科大学》2017年硕士论文

【摘要】：癌症是人类面临的一个严重的健康安全问题。目前,癌症死亡率高的有肺癌、结直肠癌、前列腺癌以及乳腺癌,这4种癌症几乎占所有癌症死亡人数的一半。在全球癌症死亡者中肺癌的新增死亡率居高不下。随着医学科学水平的发展,免疫治疗由于其创伤小且针对性强等优势,已成为继手术切除治疗以及放化疗后的一种新的肿瘤治疗方式。而寻找高效且特异的靶抗原是肿瘤免疫治疗的关键。癌/睾丸抗原(Cancer/testis antigens,CTA)在正常组织中限制性表达于睾丸组织,偶尔表达于卵巢和胎盘组织,在各种肿瘤组织中有不程度表达,具有特异的表达模式,因此,具有作为肿瘤免疫治疗特异靶点的潜在优势。近年来,本课题组一直重点探索不同肿瘤组织中黑色素瘤相关抗原(melanoma antigen,MAGE)-A家族的表达、生物学功能及作为免疫治疗靶点的可行性研究。本研究利用免疫组织化学染色法以及荧光原位杂交技术(fluorescent in situ hybridization,FISH)检测非小细胞肺癌(non-small-cell lung cancer,NSCLC)肿瘤组织及其癌旁组织中MAGE-As(包括MAGE-A1、-A2、-A3、-A4、-A6、-A10和A12)的表达、EGFR基因扩增和ALK基因重排情况以及与临床生物学指标的关系。进一步探讨了肺癌患者外周血中MAGE-As基因的表达与临床预后之间的关系。主要研究内容和结果如下:第一部分非小细胞肺癌患者肿瘤组织中MAGE-As的表达及其临床意义目的:探讨黑色素瘤相关抗原(melanoma antigen,MAGE)-As在非小细胞肺癌肿瘤组织中的表达,并分析其与患者临床病理学特征及其预后的关系。方法:1购买上海国家工程研究中心的NSCLC肿瘤组织及相应癌旁组织生物芯片各90例,应用免疫组织化学染色法检测NSCLC肿瘤组织及相应癌旁组织中MAGE-As蛋白的表达。2利用荧光原位杂交技术检测NSCLC肿瘤组织中EGFR基因扩增和ALK基因重排的情况,并分析MAGE-As表达与EGFR基因扩增和ALK基因重排之间的关系。结果:1 NSCLC肿瘤组织中MAGE-As蛋白的阳性表达率为45.56%(41/90)。2 MAGE-As蛋白的表达与患者的临床病理学特征、EGFR基因扩增和ALK基因重排均无相关性(P0.05)。3 Log-Rank检验显示,MAGE-As蛋白表达阳性的NSCLC患者的生存期均显著低于其表达阴性的患者(P=0.002)。而EGFR基因扩增和ALK基因重排与患者的整体生存率无关(P=0.309)(P=0.189)。4多因素分析结果显示,MAGE-As表达、临床分期和淋巴结转移可做为NSCLC患者预后较差的独立危险因素。结论:MAGE-As蛋白可能是NSCLC的相关抗原,MAGE-As蛋白可作为非小细胞肺癌预后不良的判定指标。第二部分肺癌患者外周血中MAGE-As基因的表达及其临床意义目的:探讨MAGE-As基因在肺癌患者外周血中的表达及其临床意义。方法:1采用多重巢式RT-PCR(multi RT-nested PCR)方法检测122例肺癌患者和30例健康人外周血中MAGE-As mRNA表达水平。2利用特异性酶切方法鉴定该家族成员MAGE-A1、-A2、-A3、-A4、和-A6的表达情况。结果:1 MAGE-As mRNA在肺癌患者外周血中表达率为17.21%(21/122),MAGE-As家族各成员在肺癌患者外周血中的表达顺序为A2A6A4A3A1。表达阳性率分别为MAGE-A1 2.46%(3/122)、MAGE-A2 15.57%(19/122)、MAGE-A3 9.02%(11/122)、MAGE-A412.30%(15/122)、MAGE-A6 13.93%(17/122)。2肺癌患者外周血中MAGE-As mRNA的表达与临床指标间的相关性。肺癌患者外周血中MAGE-As mRNA的表达与患者临床分期、肿瘤大小、淋巴结转移、远端转移、放化疗以及年龄明显相关(均P0.05)。外周血MAGE-As mRNA的表达率与肺癌患者的肿瘤类型、吸烟、喝酒无明显相关性(均P0.05)。3肺癌患者外周血中MAGE-A2、-A3、-A4和-A6 mRNA的表达与患者临床分期、肿瘤大小、淋巴结转移、远端转移有明显相关性(均P0.05)。另外,远端转移组患者外周血中MAGE-A1的表达阳性率显著高于未转移组(P0.05),放化疗后肺癌患者外周血中MAGE-A2、-A3和-A6 mRNA的表达阳性率均低于未接受放化疗的患者(均P0.05)。结论:MAGE-As mRNA在肺癌患者外周血中的表达与肺癌预后相关,有可能作为监测肺癌预后的重要指标,以及检测肺癌患者外周血循环肿瘤细胞的标记。
[Abstract]:Cancer is a serious health safety problem for human beings. At present, cancer mortality is high, including lung cancer, colorectal cancer, prostate cancer, and breast cancer. These 4 cancers account for almost half of all cancer deaths. The new mortality rate of lung cancer is high in the global cancer deaths. With the development of medical science, immunization The treatment of Cancer/testis antigens (CTA) is the key to tumor immunotherapy. Cancer / testicular antigen (CTA) is restricted to the testis tissue in normal tissues and occasionally in normal tissues. The expression in the ovarian and placental tissues is not expressed in various tumor tissues, and has a specific expression pattern. Therefore, it has a potential advantage as a specific target for tumor immunotherapy. In recent years, we have been focusing on the expression of the melanoma antigen (MAGE) -A family in the melanoma phase of different tumor tissues. This study uses immunohistochemical staining and fluorescence in situ hybridization (fluorescent in situ hybridization, FISH) to detect non small cell lung cancer (non-small-cell lung cancer, NSCLC) and MAGE-As in the para cancerous tissues of non small cell lung cancer. The expression of 0 and A12, EGFR gene amplification and ALK gene rearrangement and the relationship with clinical biological indexes. The relationship between the expression of MAGE-As gene in peripheral blood of lung cancer patients and clinical prognosis is further explored. The main contents and results are as follows: the first part is the expression of MAGE-As in the tumor tissues of non small cell lung cancer patients and The clinical significance Objective: To investigate the expression of melanoma antigen (MAGE) -As in non-small cell lung cancer tumor tissue, and to analyze its relationship with the clinicopathological features and prognosis of the patients. Methods: 1 to buy the NSCLC tumor tissue of the Shanghai National Engineering Research Center and the corresponding biochip of the corresponding paracancerous tissue in 90 cases. Immunohistochemical staining was used to detect the expression of MAGE-As protein in NSCLC tumor tissues and corresponding para cancerous tissues..2 amplification and ALK gene rearrangement in NSCLC tumor tissues were detected by fluorescence in situ hybridization, and the relationship between MAGE-As expression and EGFR gene amplification and ALK rearrangement was analyzed. Results: 1 NSCLC tumor group. The expression of the positive expression of MAGE-As protein was 45.56% (41/90).2 MAGE-As protein and the clinicopathological features of the patients. There was no correlation between EGFR gene amplification and ALK gene rearrangement (P0.05).3 Log-Rank test. The survival period of NSCLC patients with positive MAGE-As protein expression was significantly lower than that of those with negative expression (P=0.002). Gene amplification and ALK gene rearrangement and the overall survival rate of patients (P=0.309) (P=0.189).4 multivariate analysis showed that MAGE-As expression, clinical stage and lymph node metastasis could be independent risk factors for poor prognosis in NSCLC patients. Conclusion: MAGE-As protein may be the associated antigen of NSCLC, and MAGE-As protein can be used as non small cell lung cancer. Evaluation index of poor prognosis. Expression of MAGE-As gene in peripheral blood of second lung cancer patients and its clinical significance: To explore the expression and clinical significance of MAGE-As gene in peripheral blood of patients with lung cancer. Methods: 1 using multiple nested RT-PCR (multi RT-nested PCR) Fang Fajian in 122 cases of lung cancer and 30 healthy people in peripheral blood MA GE-As mRNA expression level.2 was used to identify the expression of MAGE-A1, -A2, -A3, -A4, and -A6 in the family members by specific enzyme digestion. Results: the expression rate of 1 MAGE-As mRNA in peripheral blood of lung cancer patients was 17.21% (21/122). 2.46% (3/122), MAGE-A2 15.57% (19/122), MAGE-A3 9.02% (11/122), MAGE-A412.30% (15/122), MAGE-A6 13.93% (17/122).2, the correlation between the expression of MAGE-As mRNA in peripheral blood of the lung cancer patients and the clinical staging, tumor size, lymph node metastasis, distal metastasis, radiotherapy and chemotherapy in the peripheral blood of the patients with lung cancer The expression of MAGE-As mRNA in peripheral blood has no significant correlation with tumor type, smoking and drinking (P0.05) in patients with lung cancer (all P0.05) the expression of MAGE-A2, -A3, -A4 and -A6 mRNA in patients with.3 lung cancer has a significant correlation with the clinical stages, tumor size, lymph node metastasis and distal metastasis (P0.05). The positive rate of MAGE-A1 expression in peripheral blood of patients with distal metastasis was significantly higher than that in non metastasis group (P0.05). The positive rate of MAGE-A2, -A3 and -A6 mRNA in peripheral blood of lung cancer patients after radiotherapy and chemotherapy was lower than that of patients without chemotherapy (P0.05). Conclusion: the expression of MAGE-As mRNA in peripheral blood of lung cancer patients is related to the prognosis of lung cancer, and there is a possible correlation between the expression of MAGE-As mRNA in lung cancer patients and the prognosis of lung cancer. It can be used as an important indicator for monitoring the prognosis of lung cancer and a marker for detecting circulating tumor cells in peripheral blood of patients with lung cancer.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

【参考文献】