ⅠB1-ⅡB期宫颈鳞癌癌灶中神经营养因子及受体的表达及其与临床分期的关系

发布时间：2018-05-17 03:35

本文选题：宫颈癌 + 神经营养因子　；参考：《南方医科大学》2017年硕士论文

【摘要】：神经营养因子(neurotrophin,NT)最早发现于神经系统,参与神经细胞的生长和分化,NT由神经生长因子(nerve growth factor,NGF)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)和NT-3、NT-4/5以及源自哺乳动物的NT-6和NT-7组成,目前发现的NT受体有两类,即低亲和力受体P75受体及高亲和力受体酪氨酸激酶受体(Tyrosine kinase receptor,Trk),Trk可分为3种类型,即TrkA、TrkB和TrkC,它们选择性地与不同的NT特异性结合,两类受体常在同一神经元同时表达,共同调节神经元对NT的反应。近年来,越来越多的研究表明神经营养因子及其受体与肿瘤的生长相关,包括促进肿瘤细胞增值,肿瘤细胞生存和浸润,对乳腺癌、卵巢癌、前列腺癌、大肠癌等的研究均证实了上述观点,而有关神经营养因子及其受体在宫颈癌中的研究甚少,已有的研究尚不全面,纳入的病例数有限,因此本研究主要对神经营养因子及其受体在宫颈鳞癌癌灶中的表达进行定性定量研究,并分析不同观察指标之间的关系,并进一步推断其在宫颈鳞癌的发生发展中的作用,为后续对宫颈癌发生机制的研究提供方向。第一章神经营养因子及其受体在宫颈鳞癌及正常宫颈中的表达第一节神经营养因子及其受体在正常宫颈中的表达[目的]探讨神经营养因子及其受体在正常宫颈组织中表达的定性定量情况[方法]免疫组化,生物体视学[结果](1)NGF仅表达于正常宫颈上皮的基底层细胞,为核表达,呈线状分布,表达量平均光密度值为0.0347±0.0567;BDNF表达均匀分布于正常宫颈上皮全层,为细胞膜及胞浆的共表达,表达量平均光密度值为0.2560±0.0992;P75在宫颈上皮的分布呈由基底细胞层至角化层依次递减趋势,为单纯细胞膜表达,表达量平均光密度值为0.0482±0.0239;TrkA及TrkB均匀分布于正常宫颈上皮细胞全层,呈细胞核及胞浆的共表达,表达量平均光密度值分别为0.0506±0.0390、0.1199±0.0390;(2)宫颈基质中未见神经营养因子及受体表达阳性的相关结构;[结论]神经营养因子及其受体参与了正常宫颈上皮细胞的生长,第二节神经营养因子及其受体在ⅠB1-ⅡB期宫颈鳞癌中的表达[目的]探讨神经营养因子及其受体在ⅠB1-ⅡB期宫颈鳞癌组织中表达的定性定量情况[方法]免疫组化,免疫荧光,生物体视学[结果](1)NGF主要定位于癌细胞的细胞核,阳性率为92.4%,表达量与正常宫颈上皮细胞中的表达量之间差异无统计学意义(0.0321±0.0254:0.0347±0.0567,t=-0.260,P0.05);BDNF及P75均主要定位于细胞膜,阳性率均为100%,相比于正常宫颈上皮细胞,前者表达量低(0.1409±0.0550:0.2560±0.0992,t=-4.421,P0.05),后者表达量高(0.1072±0.0694:0.0482±0.0239,t=6.797,P0.05);TrkA主要定位于胞浆,阳性表达率为96.8%,TrkB主要为膜浆共表达,阳性表达率为94.4%,相比于正常宫颈上皮细胞,前者表达量高(0.0844±0.0658:0.0506±0.0390,t=6.797,P0.05),后者表达量低(0.0421±0.0334:0.1199±0.0390,t=-4.421,P0.05);(2)神经营养因子及其特异性受体在宫颈鳞癌细胞中存在共表达的关系;(3)在宫颈鳞癌癌灶中,可见P75阳性神经纤维,阳性率为50.8%(63/124),TrkA及TrkB可见表达于癌灶内的弹性动脉管壁或脉管的内皮细胞,未见BDNF及NGF在癌灶间质的表达;(4)宫颈鳞癌中BDNF与TrkB、P75与TrkA、TrkA与TrkB表达量呈正相关关系(r=0.294,P0.05)、(r=0.452,P0.05)、(r=0.452,P0.05),其余各神经营养因子及受体表达量之间无相关关系。[结论](1)神经营养因子及其受体的表达量变化与宫颈鳞癌的发生有关,且各因子表达量之间存在相互调节的关系,共同表达于肿瘤细胞内,促进肿瘤细胞的生长(2)癌灶间质可见神经营养因子受体表达阳性的相关组织结构,表明神经营养因子受体可能影响肿瘤生长微环境。第二章宫颈鳞癌癌灶中各神经营养因子表达量及表达位置与肿瘤分期的关系[目的]研究神经营养因子及其受体的定性定量表达与分期的关系[方法]采用spearman秩相关、两个独立样本比较的Wilcoxon秩和检验、及单因素方差分析对纳入的临床病理指标与实验结果进行分析比较[结果](1)表达位置与分期:BDNF及P75膜浆共表达组分期均高于单纯膜表达组(X~2=22.841,P0.05)、(X~2=23.442,P0.05),其余因子及受体表达位置在各分期之间无差异;(2)表达量与分期:NGF表达量在ⅠB1-ⅡB期之间存在差异(F=5.303,P0.05),ⅡA2 期宫颈鳞癌表达量最高(0.0571 ±0.0281),且ⅠB1-ⅡA2期表达量与分期呈上升趋势,其余因子及受体表达量在各分期之间无差异;(3)P75受体与TrkA受体的表达量之比与分期呈负相关关系(r=-0.257,P0.05)。[结论]NGF的表达量、P75与TrkA受体的表达量之比、BDNF及P75的表达位置与宫颈鳞癌的进展相关
[Abstract]:Neurotrophin (NT) was first found in the nervous system and involved in the growth and differentiation of nerve cells. NT was composed of nerve growth factor (NGF), brain-derived neurotrophic factor, BDNF) and NT-3, and derived from mammals. There are two types, the low affinity receptor P75 receptor and the high affinity receptor tyrosine kinase receptor (Tyrosine kinase receptor, Trk), and Trk can be divided into 3 types, namely TrkA, TrkB and TrkC, which selectively bind to different NT specifically. The two types of receptors are often expressed at the same time in the same neuron and jointly regulate the reaction of neurons to NT. In recent years, the more The more studies have shown that neurotrophic factors and their receptors are associated with tumor growth, including the promotion of tumor cell proliferation, tumor cell survival and infiltration, and studies on breast, ovarian, prostate and colorectal cancer, which have been confirmed, and there are few studies on neurotrophic factors and their receptors in cervical cancer. The study is not comprehensive and the number of cases included is limited. Therefore, this study mainly studies the expression of neurotrophic factor and its receptor in cervical squamous cell carcinoma, and analyzes the relationship between different observation indexes, and further infer its role in the development of cervical squamous cell carcinoma, in order to follow up the mechanism of cervical cancer. The expression of neurotrophic factor and its receptor in cervical squamous cell carcinoma and normal cervix; the expression of the first neurotrophic factor and its receptor in the normal cervix [Objective] to investigate the qualitative and quantitative analysis of neurotrophic factors and their receptors in normal cervical tissues. Results: (1) the expression of NGF was only expressed in the basal layer cells of normal cervical epithelium, which was nuclear expression and linear distribution, and the average density of the expression was 0.0347 + 0.0567. The expression of BDNF was evenly distributed in the whole layer of normal cervical epithelium and co expressed in the cell membrane and cytoplasm. The average density of the expression was 0.2560 + 0.0992, and the distribution of P75 in the cervical epithelium was presented. The basal cell layer to keratinized layer descended in turn, which was a simple cell membrane expression, and the average density of the expression was 0.0482 + 0.0239. TrkA and TrkB were evenly distributed in the whole layer of normal cervical epithelial cells, presenting the co expression of the nucleus and cytoplasm, and the mean optical density of the expression was 0.0506 + 0.0390,0.1199 + 0.0390, respectively. (2) the cervical matrix was not found. Neurotrophic factor and receptor expression related structure; [Conclusion] neurotrophic factor and its receptor are involved in the growth of normal cervical epithelial cells. The expression of second ganglion neurotrophic factor and its receptor in stage I B1- II B cervical squamous cell carcinoma (objective) to investigate the expression of neurotrophic factor and its receptor in stage I B1- II B cervical squamous cell carcinoma The qualitative and quantitative situation [method], immunofluorescence, immunofluorescence, and biological vision (1) NGF were mainly located in the nucleus of cancer cells, the positive rate was 92.4%. There was no significant difference between the expression and the expression of normal cervical epithelial cells (0.0321 + 0.0254: 0.0347 + 0.0567, t=-0.260, P0.05); BDNF and P75 were mainly located in the cells. The positive rate of cell membrane was 100%. Compared to normal cervical epithelial cells, the expression of the former was low (0.1409 + 0.0550:0.2560 + 0.0992, t=-4.421, P0.05), the latter was high (0.1072 + 0.0694:0.0482 + 0.0239, t=6.797, P0.05); TrkA was mainly located in the cytoplasm, the positive expression rate was 96.8%, TrkB was mainly expressed in membrane plasma, and the positive expression rate was 94.4%. Compared to normal cervical epithelial cells, the expression of the former was high (0.0844 + 0.0658:0.0506 + 0.0390, t=6.797, P0.05), the latter was low (0.0421 + 0.0334:0.1199 + 0.0390, t=-4.421, P0.05), and (2) the relationship between neurotrophic factor and its specific receptor in cervical squamous cell carcinoma cells; (3) in the squamous carcinoma of cervix, the P75 positive God was found. The positive rate was 50.8% (63/124), TrkA and TrkB were found in the endothelial cells of the elastic artery wall or pulse tube in the cancer, and no expression of BDNF and NGF in the cancer range; (4) BDNF and TrkB, P75 and TrkA, TrkA and TrkB expression in cervical squamous cell carcinoma were positively correlated (r=0.294,), and the rest of the gods. There is no correlation between the operating factor and the expression of the receptor. [Conclusion] (1) the expression of neurotrophic factor and its receptor is related to the occurrence of squamous cell carcinoma of the cervix, and there is a relationship between the expression of each factor and the expression of each factor in the tumor cells to promote the growth of cancer cells (2) the neurotrophic factor of the cancer range is visible. The related tissue structure of receptor positive expression indicates that neurotrophic factor receptor may affect the microenvironment of tumor growth. Second the relationship between the expression of neurotrophic factors and the expression position of neurotrophic factors in the squamous cell carcinoma of the cervix and the relationship between the tumor staging and the relationship [Objective] to study the relationship between the quantitative expression of neurotrophic factor and its receptor and its staging The Spearman rank correlation, the Wilcoxon rank sum test of two independent samples, and the single factor analysis of variance analysis were used to analyze the included clinicopathological indexes and experimental results. [results] (1) the expression position and staging of BDNF and P75 membrane plasma co expression group were higher than that of the simple membrane surface (X~2=22.841, P0.05), (X~2=23.442, P0.05), and the other factors. There was no difference in the expression position between the substages and the substages. (2) the expression amount and the stage of the expression of NGF were different (F=5.303, P0.05), and the expression of cervical squamous cell carcinoma in stage II A2 was the highest (0.0571 + 0.0281), and the expression of I B1- II A2 stage was on the rise and the expression of the other factors and receptors had no difference between the stages. (3) the ratio of P75 receptor to TrkA receptor is negatively correlated with staging (r=-0.257, P0.05). [conclusion the expression of]NGF, the ratio of P75 to TrkA receptor, the expression of BDNF and P75, is related to the progression of squamous cell carcinoma of the cervix.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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