血管生成素样蛋白5在人胃癌组织中的表达及临床意义

发布时间：2018-06-29 15:27

本文选题：胃肿瘤 + ANGPTL5　；参考：《山东大学》2017年硕士论文

【摘要】：[研究背景]胃癌(Gastric cancer,GC)于全球极为常见,虽然近年来GC的发病率有所降低,但其死亡率仍高居第二。我国为GC高发地区,发病率及死亡率分别位于国内第二及三位;造成这种严峻结果的原因大都为多数患者就诊时已为疾病进展期,且目前进展期的治疗效果仍不佳;虽然分子靶向药物在GC中的应用取得了较好的疗效,但由于其异质性高,效果仍不尽如人意。因此,研究其发生发展机制以期发现新的靶点对该疾病的诊断和治疗具有非常重要的意义。血管生成素样蛋白5(angiopoietin-like protein 5,ANGPTL5)是一类新的分泌性糖蛋白家族——血管生成素样蛋白家族(angiopoietin-like proteins,ANGPTLs)的成员之一,ANGPTL5 主要表达于成人心肌组织,目前对其功能的研究主要集中在脂质代谢及干细胞方面,ANGPTLs对甘油三酯的代谢具调节作用,ANGPTL5基因的功能失活突变可下调血浆中甘油三酯水平,ANGPTL5也可促进造血干细胞的有效扩增,并能维持干细胞的移植再生及多向分化等能力。研究证实,ANGPTL5在实体肿瘤NSCLC及血液肿瘤AMIL中高表达,且与两者肿瘤细胞的分化程度相关,而在其他肿瘤中的表达及意义尚未明确。因此,本课题拟研究ANGPTL5在胃癌组织及癌旁正常组织中的表达及临床意义,以期为GC的治疗提供新的潜在靶点。[研究目的]检测ANGPTL5在胃癌组织及癌旁正常组织中的表达方式及表达水平,分析ANGPTL5在两者中表达的差异;进而分析ANGPTL5与胃癌患者多种临床病理的参数及与其总生存期(overall survival,OS)的关系。检测在上述胃癌组织的样本中CD34的表达水平,并分析样本组织中ANGPTL5的表达水平与微血管密度(microvessel density,MVD)的关系,尝试探索ANGPTL5在GC发生发展过程中的作用。[研究方法]1.收集山东大学附属济南市中心医院2009年12月到2011年8月73例患者的胃癌组织及相应癌旁正常组织,采用免疫组织化学染色(Immunohistochemistry,IHC)法检测ANGPTL5蛋白在两类样本中的表达方式和表达水平,以及CD34在73例胃癌组织中的表达水平。2.采用卡方检验分析ANGPTL5蛋白在两类样本中表达水平的差异,采用卡方检验、连续校正的卡方检验方法分析ANGPTL5的表达与临床病理参数间及其与MVD的相关性;绘出生存曲线并应用Log-rank方法检验ANGPTL5的表达与OS的关系。[结果]1.ANGPTL5蛋白主要定位于样本肿瘤细胞的胞质,阳性呈棕褐色弥漫性分布,胞膜及胞核偶见较浅着色,少数间质细胞的胞质中为浅黄色的弱表达。其癌旁的正常组织中,ANGPTL5于部分细胞的胞浆中呈浅黄色弥漫性的表达。2.ANGPTL5蛋白在胃癌组织中的表达(48/73)明显高于其在对应癌旁的正常组织中的表达水平(11/73)(χ2=38.939,P0.001)。3.ANGPTL5在肿瘤组织中的表达水平与原发肿瘤的大小(χ2=5.006,P=0.025)、肿瘤的浸润深度(χ2=6.810,P=0.009)和肿瘤的TNM分期(χ2=4.867,P=0.027)呈正相关;而与性别、肿瘤细胞分化程度、年龄、淋巴结转移无明显相关(P0.05)。4.在胃癌组织中ANGPTL5蛋白的表达水平与MVD的表达呈明显正相关(R=0.480,P0.001)。5.73例中ANGPTL5阳性患者的OS明显短于ANGPTL5阴性患者(χ2=5.888,P=0.015)。[结论]ANGPTL5在胃癌组织中高表达,与胃癌的浸润深度、原发肿瘤大小、TNM分期相关,更重要的是,ANGPTL5与MVD有明显的正相关,与总生存时间呈显著负相关。提示,ANGPTL5可能肿瘤的血管生成有关,参与了胃癌的发生发展过程,有可能成为胃癌的潜在预后不良因子。
[Abstract]:[background] Gastric cancer (GC) is very common in the world. Although the incidence of GC has been reduced in recent years, the mortality rate is still high second. China is a high incidence area of GC, the incidence and mortality rate are located at second and three in China, and most of the reasons for this severe result are the disease progression period in most patients. The therapeutic effect of the current progressing stage is still poor; although the molecular targeting drug has achieved good therapeutic effect in GC, the effect is not satisfactory because of its high heterogeneity. Therefore, it is very important to find new targets for the diagnosis and treatment of the disease. 5 (angiopoietin-like protein 5, ANGPTL5) is one of the new secretory glycoprotein family members of the family of angiopoietin-like proteins (ANGPTLs), and ANGPTL5 is mainly expressed in adult cardiac muscle tissue. The research on its function is mainly focused on lipid metabolism and stem cells, ANGPTLs against glycerol three. The metabolism of the ester has a regulating effect. The functional inactivation mutation of the ANGPTL5 gene can down regulate the level of triglyceride in the plasma. ANGPTL5 can also promote the effective amplification of hematopoietic stem cells, and can maintain the ability of stem cells to be transplanted and regenerated and multidirectional differentiation. The study confirms that ANGPTL5 is highly expressed in the solid tumor NSCLC and the blood tumor AMIL, and is associated with both swelling and swelling. The degree of differentiation of the tumor cells is related, and the expression and significance in other tumors are not clear. Therefore, this topic intends to study the expression and clinical significance of ANGPTL5 in gastric cancer tissues and normal tissues adjacent to cancer in order to provide new potential targets for the treatment of GC. [Objective] to detect the expression of ANGPTL5 in gastric cancer tissues and normal tissues adjacent to cancer. The expression level and the expression level of ANGPTL5 were analyzed, and the relationship between the various clinical and pathological parameters and the total survival time (overall survival, OS) of ANGPTL5 and gastric cancer patients was analyzed. The expression level of CD34 in the samples of the above gastric cancer tissue was detected, and the expression level of ANGPTL5 and the microvessel density in the sample tissues were analyzed. (microvessel density, MVD) relationship, try to explore the role of ANGPTL5 in the development of GC. [research method]1. collect 73 cases of gastric cancer tissue and corresponding normal tissue adjacent to cancer in Ji'nan Center Hospital Affiliated to Shandong University from December 2009 to August 2011, and use immunohistochemical staining (Immunohistochemistry, IHC) method to detect ANG. The expression and expression level of PTL5 protein in two types of samples, and the expression level of CD34 in 73 cases of gastric cancer tissue,.2. used chi square test to analyze the difference in the expression level of ANGPTL5 protein in the two samples. The chi square test and the continuous correction of the chi square test were used to analyze the expression of ANGPTL5 and the clinicopathological parameters and MVD The relationship between the expression of the survival curve and the Log-rank method was used to test the relationship between the expression of ANGPTL5 and the expression of OS. [results]1.ANGPTL5 protein was mainly located in the cytoplasm of the tumor cells of the sample, and the positive was brown diffuse distribution, and the cytoplasm of the cytoplasm of a few stromal cells was light yellow. In the tissue, the expression of ANGPTL5 in the cytoplasm of some cells was light yellow and diffuse expression of.2.ANGPTL5 protein in gastric cancer tissue (48/73) was significantly higher than that in normal tissues adjacent to the carcinoma (11/73) (x 2=38.939, P0.001).3.ANGPTL5 in the tumor tissue and the size of the primary tumor (Chi 2=5.006, P=0.025) The depth of tumor infiltration (x 2=6.810, P=0.009) was positively correlated with the TNM staging of the tumor (x 2=4.867, P=0.027), but there was no significant correlation with sex, the degree of differentiation, age, and lymph node metastasis (P0.05) the expression of ANGPTL5 protein in gastric cancer tissues was positively correlated with the expression of MVD (R=0.480, P0.001) in.5.73 cases. The OS of the patients was significantly shorter than the ANGPTL5 negative patients (x 2=5.888, P=0.015). [conclusion the high expression of]ANGPTL5 in gastric cancer tissue is related to the depth of gastric cancer, the size of the primary tumor, the TNM staging, and more importantly, there is a significant positive correlation between ANGPTL5 and MVD and a significant negative correlation with the total survival time. Guan is involved in the occurrence and development of gastric cancer, and may become a potential prognostic factor for gastric cancer.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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