自噬基因Bedin-1在前列腺癌组织中的表达及意义

发布时间：2018-03-23 03:31

本文选题：前列腺癌　切入点：细胞自噬　出处：《安徽医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：细胞自噬(Autophagy)是一个广泛存在于真核细胞中的重要的生理过程,主要方式为细胞初级溶酶体处理内源性底物,包括细胞清除废物、重建结构以及生长发育。生命体借此维持蛋白代谢平衡及细胞内环境稳定,并与疾病的发生密切相关。目前,学术界公认的自噬主要形式有:巨自噬(macroautophagy),微自噬(microautophagy),以及分子伴侣介导的自噬(chaperone mediated autophagy,CMA)。巨自噬即是我们通常所称的自噬。目前已知的自噬调控途径有:Beclin-1信号途径;mTOR(Mammalian Target of Rapamycin)信号途径;自噬相关基因(Autophagy Related Gene,Atg)与泛素样结合系统(Ubiquitin-link system)。其中,自噬基因Beclin-1与酵母自噬基因Atg6同源,位于染色体17q21,定位于高尔基体参与哺乳动物自噬体的形成,是介导其他自噬蛋白定位于前自噬小体的关键因子。前列腺癌(Prostate Cancer,PCa)是当今社会常见的男性恶性肿瘤。近年来,其发病率在我国男性人群中呈逐年攀高趋势。晚期前列腺癌的治疗大多依赖于去除雄激素方法。然而,绝大多数患者最终会转变为雄激素抵抗型前列腺癌(Castrate-Resistant Prostate Cancer,CRPC),导致对传统的去势治疗反应效果不佳。相关研究已经初步证明自噬在CRPC中扮演着重要角色,而自噬基因Beclin-1在多种肿瘤组织中呈低水平表达,预示着细胞自噬在前列腺癌的发生、发展、转归中发挥着作用。本课题采用免疫组化的方法检测Beclin-1在前列腺癌组织中的表达并探讨其与相关临床、病理因素的关系。本研究取用经直肠前列腺穿刺活检术后的病理标本,共132例,所有标本均经病理证实为前列腺腺癌。本研究实验组即为前列腺腺癌组织,对照组即为良性前列腺增生组织。纳入研究的每例标本均至少有一针为良性前列腺增生组织(即癌旁组织)。对132例患者的全部穿刺标本行免疫组化染色,若其中有任何一针染色呈阳性表达,即可纳入相应的阳性组;若全部为阴性表达,则纳入相应的阴性组。采用免疫组化Super Vision两步法检测132例前列腺癌组织及癌旁组织中Beclin-1的表达,并分析其与相关临床因素的关系。结果发现:1.Beclin-1染色阳性物质呈棕黄色,表达位于细胞浆。在132例前列腺穿刺活检的病理组织中,癌旁组织的Beclin-1阳性表达率为54.5%,肿瘤组织的Beclin-1阳性表达率为38.6%,明显低于其在癌旁组织中的表达。2.本研究将132例前列腺癌穿刺标本按术后Gleason评分不同分为三组:2~4分;5~7分;8分以上。Beclin-1在三组中的阳性表达率分别为66.7%,39.7%,27.3%,评分越高,表达率越低,组间差异具有统计学意义。3.Beclin-1的表达差异与是否发生淋巴结转移、是否发生骨转移有关,具有统计学意义(P0.05);而与年龄、是否具有家族史及前列腺炎病史差异均无统计学意义(P0.05)。4.在全部132例前列腺癌患者中,有76例进行了根治性前列腺切除术,术后三个月进行随访,检测PSA水平,有10例≥0.02ng/ml,66例0.02ng/ml。在PSA0.02ng/ml的66例中有42例Beclin-1表达阳性,阳性率为63.6%,而在PSA≥0.02ng/ml的10例中,2例Beclin-1表达为阳性,阳性率为20%,明显低于前者(P0.05)。以上研究提示,自噬基因Beclin-1在前列腺癌组织中表达下调,并与淋巴结转移、骨转移及生化复发有关,其表达下调可能参与前列腺癌的发生、发展,为前列腺癌的诊断及治疗提供了新的思路。
[Abstract]:Autophagy (Autophagy) is a widespread important physiological processes in eukaryotic cells, the main way for cell lysosomes processing endogenous substrates, including the removal of waste cells, reconstruction of structure and growth life. To maintain the balance of protein metabolism and cell homeostasis, and is closely related with the occurrence of the disease at present. Autophagy, mainly in the form of academic circles have been recognized: macroautophagy (macroautophagy), microautophagy (microautophagy), as well as molecular chaperone mediated autophagy (chaperone mediated, autophagy, CMA). The giant autophagy is that we are often called autophagy. Currently autophagy pathways known: Beclin-1 signaling pathway; mTOR (Mammalian Target of Rapamycin) signaling pathway of autophagy related genes (Autophagy, Related; Gene, Atg) system combined with ubiquitin like (Ubiquitin-link system). Among them, the autophagy gene Beclin-1 and yeast from Phage Atg6 homologous gene, located on chromosome 17q21, forming localized in the Golgi in mammalian autophagy, is a key factor mediated autophagy protein located in the other before the autophagosome. Prostate cancer (Prostate Cancer PCa) is a common malignant tumor in male society. In recent years, the incidence in the male population in China was gradually rising trend. In the treatment of advanced prostate cancer mainly depends on androgen removal methods. However, most patients eventually transformed into androgen resistant prostate cancer (Castrate-Resistant Prostate Cancer, CRPC), resulting in the effect of castration in response to the traditional poor. Studies have proved that autophagy plays an important role in CRPC, and autophagy gene Beclin-1 in various tumor tissues showed low expression indicates that autophagy in prostate carcinogenesis, development, to play a role Expression. The method of immunohistochemical detection of Beclin-1 in prostate cancer tissues and to explore its relationship with clinical and pathological factors. This study used by pathology after transrectal prostate biopsy, a total of 132 cases, all specimens were pathologically confirmed prostate adenocarcinoma in this research. The experimental group is prostate adenocarcinoma, the control group is the benign prostatic hyperplasia. Every case were included in the study were at least one needle for benign prostatic hyperplasia (i.e. carcinoma). With the color of 132 patients with biopsy specimens of all immune groups, if there is any one positive expression that can be put into the corresponding positive group; if all the negative, are included in the negative group. The corresponding expression of Beclin-1 Super Vision two step method for detection of prostate cancer and 132 cases of carcinoma tissues, and analyze the The relationship and clinical factors. The results showed that 1.Beclin-1 positive staining material was brown, expression located in the cytoplasm. In 132 cases of pathological biopsy of the prostate, the positive expression of Beclin-1 in tissue adjacent to carcinoma was 54.5%, the positive expression of Beclin-1 in tumor tissues was 38.6%, was significantly lower than that in the adjacent tissues the expression of.2. in this study, 132 cases of prostate cancer biopsy specimens according to postoperative Gleason score were divided into three groups: 2~4; 5~7; expression of more than 8.Beclin-1 in the three groups in the rates were 66.7%, 39.7%, 27.3%, the higher the score, the expression rate is low, the difference between the groups was statistically difference expression the significance of.3.Beclin-1 and incidence of lymph node metastasis, whether the occurrence of bone metastasis, with statistical significance (P0.05); and whether there is difference with age, medical history and family history of prostatitis were not statistically significant (P0.05.4.) in all 132 Patients with prostate cancer, 76 cases of radical prostatectomy were followed up three months after operation, testing the levels of PSA, 10 cases of more than 0.02ng/ml and 0.02ng/ml. in 66 cases in PSA0.02ng/ml 66 cases in 42 cases of Beclin-1 positive expression, the positive rate was 63.6%, while in PSA over 0.02ng /ml 10 in the cases, 2 cases of positive Beclin-1 expression, the positive rate was 20%, significantly lower than the former (P0.05). These studies suggest that expression of autophagy gene Beclin-1 in prostate cancer with lymph node metastasis and reduction, bone metastasis and biochemical recurrence is related to the down-regulation of its expression may be involved in prostate carcinogenesis, development, provide new ideas for the diagnosis and treatment of prostate cancer.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R737.25

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