Bcl2、Caspase3在人脑胶质瘤中的表达及意义

发布时间：2018-04-29 18:10

  本文选题：人脑胶质瘤 + 细胞凋亡　； 参考：《河北医科大学》2014年硕士论文

【摘要】：目的：人脑胶质细胞瘤脑简称胶质瘤,是人类中枢神经系统中最常见的恶性肿瘤之一。由于它呈侵袭性生长，使得临床治疗困难，是导致病人死亡的主要原因。我国是胶质瘤的高发国家，每年的发病人数和因胶质瘤而死亡人数都位居各种恶性肿瘤的前列，由于它的侵袭性生长，在治疗上成为一个世界性难题。肿瘤的发生和发展是多因素、多基因、综合作用的结果。胶质瘤是颅内主要的原发性肿瘤[1]，与多种凋亡基因，，原癌基因，抑癌基因与胶质瘤的发生有关，这些基因作用在肿瘤细胞增殖和凋亡的不同环节，凋亡抑制或平衡失调，可导致肿瘤细胞过度增殖，决定肿瘤的生长、转移和预后。目前研究证实，在多种肿瘤的发生、发展，侵袭和转移的机制中，许多细胞粘附分子和水解蛋白酶发挥重要作用，其作用机制也陆续被阐明，但与胶质瘤的关系报道并不多，因此，关于胶质瘤的发生、发展，浸润生长等机制的研究有必要从分子水平着手。 细胞凋亡是细胞在各种死亡信号刺激后发生的一系列瀑布式的主动性死亡过程，受多种基因调控。与caspase3家族和bcl2家族密切相关。肿瘤细胞的凋亡，增殖和抗凋亡的相互作用，决定肿瘤生物学行为的恶性进展程度。目前研究较多的是caspase3与bcl2在消化道肿瘤（如胃癌、肝癌、结肠癌、胰腺癌等）和泌尿生殖系肿瘤（如乳腺癌、子宫癌、卵巢癌、肾癌、膀胱癌等）中的表达，而在脑胶质瘤中的表达研究还比较少。脑胶质瘤为常见的颅内肿瘤,深入研究caspase3和bcl2在脑胶质瘤中的表达及其与脑胶质瘤临床病理分型之间的关系,可能成为脑胶质瘤的诊断、预后、治疗的一条新途径。本课题通过检测caspase3，Bcl2在不同级别脑胶质瘤中的表达以探讨caspase3，Bcl2对脑胶质瘤发生、发展及预后的意义。 方法：收集2012年12月至2013年4月于河北医科大学第二医院神经外科手术切除的人脑胶质瘤标本60例。按照WHO2007年中枢神经系统肿瘤分类，Ⅰ~Ⅱ级为低级别胶质瘤，共23例； Ⅲ~Ⅳ级为高级别胶质瘤，共37例，均有完整病历资料并经本院病理科证实。另取11例因外伤或者脑出血而进行的颅内减压的正常脑组织标本作为对照。胶质瘤患者于手术前均未进行放化疗等任何抗肿瘤治疗。所有标本均在手术切下组织后立即取材，分别于10%的福尔马林固定及液氮保存，采用免疫组织化学法IHC和RT-PCR分别检测Bcl2、Caspase3在胶质瘤中蛋白水平和mRNA水平的表达情况。实验结果数据用SPSS16.0软件进行统计学分析。 结果： 1IHC结果显示:Bcl2在正常脑组织、低、高级别胶质瘤组表达阳性率分别为9%、78%、100%；Caspase3表达阳性率分别为0%、100%、84%。Bcl2、Caspase3在三组间表达有显著性统计学差异（P=0.000），组间两两比较均有显著性统计学差异（P＜0.05），随肿瘤恶性程度增高，Bcl2表达量增高，Caspase3表达量减少。Bcl2和Caspase3在正常脑组织、低、高级别胶质瘤三组中表达呈负相关（r=-0.814，P=0.000），在其余组间表达未见相关关系，可能与样本量少有关。 2RT-PCR结果显示：Bcl2、Caspase3在正常脑组织、低、高级别胶质瘤三组间表达有显著性统计学差异（P＜0.05），组间两两比较均有显著性统计学差异（P＜0.05），随肿瘤恶性程度增高，Bcl2表达量增高，Caspase3表达量减少。并且Bcl2和Caspase3在正常脑组织、低、高级别胶质瘤三组中表达呈负相关（r=-0.254, P=0.032），在肿瘤组（包括低、高级别胶质瘤）表达也呈负相关（r=-0.48，P=0.000），在其余组中按P＜0.05检验水准下未见相关性。 结论： 1Bcl2在正常脑组织、低、高级别胶质瘤组三组间及组间两两比较表达有显著性统计学差异，随肿瘤恶性程度增高，Bcl2表达量增高，在高级别胶质瘤中表达水平最高，与胶质瘤的恶性程度相关。 2Caspase3在正常脑组织、低、高级别胶质瘤组三组间及组间两两比较表达有显著性统计学差异，随肿瘤恶性程度增高，Caspase3表达量减少，在低级别胶质瘤中表达水平最高，与胶质瘤的恶性程度相关。 3Caspase3的表达下调与胶质瘤的恶性进展关系密切，Bcl2在胶质瘤的发生、发展过程中起重要作用。Caspase3和Bcl2可能成为胶质瘤预后判断的潜在指标。 4Caspase3和Bcl2在胶质瘤中的表达存在相关性，随着Caspase3的表达下调，Bcl2的表达上调。
[Abstract]:Objective: human glioblastoma, called glioma, is one of the most common malignant tumors in the human central nervous system. It is a major cause of death because of its invasive growth and difficult clinical treatment. China is a country with high incidence of glioma, and the number of patients and the number of deaths due to glioma are all in the place of each year. The forefront of malignant tumors, due to its invasive growth, has become a worldwide problem in the treatment of cancer. The occurrence and development of tumor are the results of multiple factors, multiple genes and comprehensive effects. Glioma is the primary primary tumor of the intracranial [1], which is related to the occurrence of a variety of apoptotic genes, proto oncogenes, tumor suppressor genes and glioma. In the different links of tumor cell proliferation and apoptosis, apoptosis inhibition or imbalance can lead to overproliferation of tumor cells and determine tumor growth, metastasis and prognosis. The mechanism has been clarified, but there are few reports on the relationship between glioma and glioma. Therefore, it is necessary to study the mechanism of the occurrence, development and infiltration of glioma from the molecular level.
Cell apoptosis is a series of waterfall active death processes that occur after various death signals, which are regulated by a variety of genes. It is closely related to the Caspase3 family and the BCL2 family. The apoptosis, proliferation and anti apoptosis interaction of tumor cells determine the malignant progression of tumor biology. At present, more research is on CA. Spase3 and BCL2 are expressed in digestive tract tumors (such as gastric cancer, liver cancer, colon cancer, pancreatic cancer, etc.) and urogenital tumors (such as breast, uterine, ovarian, renal, bladder cancer), while the expression in glioma is still less. Glioma is a common intracranial tumor, and Caspase3 and BCL2 are deeply studied in glioma. The relationship between the expression and the clinicopathological classification of glioma may be a new approach for the diagnosis, prognosis and treatment of glioma. This topic is to explore the significance of Caspase3 and Bcl2 to the occurrence, development and prognosis of glioma by detecting the expression of Caspase3 and Bcl2 in different levels of glioma.
Methods: 60 cases of glioma resection in Department of Neurosurgery, Second Hospital of Hebei Medical University from December 2012 to April 2013, were collected in the Department of Neurosurgery, Second Hospital of Hebei Medical University. According to the classification of central nervous system tumor, grade I ~ II was low grade glioma in 23 cases, grade III ~ IV was high grade glioma, a total of 37 cases had complete medical records and had been treated by our hospital. The normal brain tissue specimens from 11 cases of intracranial decompression due to trauma or cerebral hemorrhage were taken as control. The patients with glioma were not treated with radiotherapy and chemotherapy before operation. All specimens were harvested immediately after surgical removal of the tissue, respectively, in 10% of the formalin fixation and the preservation of liquid nitrogen, using the immune group. The expression of protein level and mRNA level of Bcl2 and Caspase3 in glioma was detected by IHC and RT-PCR, respectively. The results of the experimental data were statistically analyzed by SPSS16.0 software.
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