食管鳞状细胞癌组织中CCL26的表达及临床意义
发布时间：2018-08-13 18:19
【摘要】：背景与目的食管癌是世界上常见的恶性消化道肿瘤之一,具有明显的侵袭性。在我国尤为高发,其分布有着明显的区域性特征,尤其是在太行山一带,如河南省安阳市林州以及毗邻的辉县市更是食管癌的高发地区。明显的家族聚集现象是该地区食管癌发病的重要特征之一,这提示着食管癌的发生和基因的易感性有关。食管癌的组织学类型主要以鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)为主。流行病学资料显示,吸烟、酗酒、不合理的饮食习惯、微量元素缺乏等环境因素和食管鳞状细胞癌的发生发展也有着密切的关系。食管癌的预后不佳,有调查研究表明,食管鳞状细胞癌在世界许多国家的5年总生存率大约只有15%左右,严重威胁着人类的身心健康。而造成其预后差、生存率低的主要原因之一就是缺乏可靠的早期检测指标和早期个体化的治疗。所以,探索研究与食管癌的发生、发展相关的癌基因、抑癌基因、分子学机制等对于食管癌的早发现、早诊断、早治疗以及提高食管癌的生存率更加重要。趋化因子是由白细胞分泌的可溶性小分子蛋白,其分子量为8~14k Da,属于小蛋白类的超家族,由于其在体内可以操纵白细胞的移行而被人们熟知,比如嗜酸性粒细胞向CCL11的迁移、中性粒细胞向CXCL8的迁移等。趋化因子和与它同源的G蛋白偶联受体相结合,从而介导一系列的细胞生物学效应,从而在调控免疫细胞的分化、发育及定向迁移等方面起到重要的作用。趋化因子与人类炎症、肿瘤的发生、发展密切相关,长期的刺激因素(如细菌、病毒等)所导致的慢性炎症,可以使机体发生癌前病变的几率大大增加,进而促进肿瘤的形成。同时,趋化因子还可以通过多种方式如自分泌或旁分泌等来诱导血管的发生,维持肿瘤生长,甚至帮助肿瘤细胞逃避机体的免疫监测等,总之,趋化因子在肿瘤发生发展过程中起着至关重要的作用。CCL26也可称之为Eotaxin-3,又称巨噬细胞炎性蛋白(Macrophage inflammatory protein 4-alpha),该基因位于染色体7q11.2,诱导小细胞因子亚家族A,成员26(SCYA26),是CC类趋化因子家族中的一员,作用于嗜酸性粒细胞、T细胞;受体为CCR3。趋化因子受体及其相应配体已被证明在恶性肿瘤的发生、发展中发挥重要的作用,CCL26能够介导炎性细胞的趋化、肿瘤细胞的增殖等生理病理过程,同时在调节肿瘤细胞的生长能力和转移能力方面也起着重要的作用。本实验采用免疫组织化学方法检测了趋化因子CCL26在ESCC组织和癌旁正常食管粘膜组织中的表达水平,目的在于进一步了解CCL26表达水平与食管鳞状细胞癌的发生、发展以及预后的关系,为研究食管癌的发病、转移、判断预后提供新的参考资料。材料与方法1.197例ESCC组织及相应的癌旁正常黏膜组织(距离肿块组织大于5cm)均收集自2005年1月—2009年12月期间在食管癌高发地区林州市人民医院的手术切除患者,全部的组织切片均经组织病理学检测确诊为食管鳞状细胞癌,所有的患者于术前均未曾接受过任何的放、化疗等治疗。2.利用组织微阵列技术制作组织芯片,采用免疫组织化学法分析197例食管鳞癌组织和癌旁相应正常黏膜组织中CCL26的表达情况。3.应用SPSS17.0统计软件包对数据进行统计分析。分类资料采用χ2检验,对食管鳞癌中CCL26的表达与患者性别、年龄、临床分期、组织类型、淋巴结转移等指标的相关性进行分析,检验水准为α=0.05;Kaplan-Meier分析CCL26的表达和食管鳞癌患者的生存关系,以P0.05表示差异有统计学意义。结果1.CCL26在食管癌组织及癌旁正常组织中均有表达,在食管癌组织中CCL26的阳性表达率为61.8%,明显高于癌旁正常组中的表达率(20.6%),差异有统计学意义(P0.05)。2.CCL26的表达与淋巴结转移有关,而与患者的性别、年龄、肿瘤细胞的分化程度和大体分型等无关(P0.05)。3.从五年生存率曲线图可以看出,CCL26阳性表达的食管鳞状细胞癌患者的5年生存率明显低于CCL26阴性表达的患者。结论1.CCL26的高表达可能在ESCC的发生、发展中发挥着重要的作用。CCL26的表达与组织学类型、细胞分化程度、TNM分期等无明显相关,而与淋巴结转移有关。由此推断,CCL26阳性表达的食管鳞癌可能具有更大的侵袭、转移能力,从而可以导致5生存率的下降。2.ESCC患者CCL26的表达情况可能作为其临床预后指标之一,检测CCL26的表达情况对ESCC的诊断、预后有一定的临床价值。由于CCL26发挥作用有着其复杂性,对ESCC中CCL26高表达的机制以及其信号通路还需要做进一步的研究。
[Abstract]:BACKGROUND & OBJECTIVE Esophageal cancer is one of the most common malignant gastrointestinal cancers in the world, which is highly aggressive. Especially in China, its distribution has obvious regional characteristics, especially in the Taihang Mountains, such as Linzhou in Anyang City, Henan Province, and Huixian City adjacent to it. Esophageal squamous cell carcinoma (ESCC) is the main histological type of esophageal cancer. Epidemiological data show that smoking, alcohol abuse, unreasonable eating habits, trace element deficiency and other environmental factors. The prognosis of esophageal squamous cell carcinoma is poor. Investigation shows that the 5-year overall survival rate of esophageal squamous cell carcinoma in many countries is only about 15%, which seriously threatens the physical and mental health of human beings. Therefore, exploring and researching the oncogene, tumor suppressor gene and molecular mechanism related to the occurrence and development of esophageal cancer is more important for early detection, early diagnosis, early treatment and improving the survival rate of esophageal cancer. Molecular proteins, with molecular weights ranging from 8 kDa to 14 kDa, belong to the superfamily of small proteins. They are well known for their ability to manipulate leukocyte migration in vivo, such as eosinophils migrating to CCL11 and neutrophils migrating to CXCL 8. Chemokines bind to other homologous G protein-coupled receptors, thereby mediating a series of fine particles. Chemokines play an important role in regulating the differentiation, development and directional migration of immune cells. Chemokines are closely related to human inflammation, tumorigenesis and development. Chronic inflammation caused by long-term stimulating factors (such as bacteria, viruses, etc.) can greatly increase the probability of precancerous lesions in the body. At the same time, chemokines can induce angiogenesis, maintain tumor growth, and even help tumor cells escape immune surveillance. In short, chemokines play an important role in the development of tumor. CCL26 can also be called Eotaxin-26. 3. Macrophage inflammatory protein 4-alpha, located on chromosome 7q11.2, induces small cytokine subfamily A, member 26 (SCYA26), a member of the CC chemokine family, acting on eosinophils, T cells; receptor CCR3. Chemokine receptors and their corresponding ligands have been shown to be malignant. CCL26 plays an important role in the occurrence and development of sex tumors. CCL26 can mediate the chemotaxis of inflammatory cells and the proliferation of tumor cells. It also plays an important role in regulating the growth and metastasis of tumor cells. The expression level of CCL26 in normal esophageal mucosa adjacent to carcinoma was studied in order to understand the relationship between the expression level of CCL26 and the occurrence, development and prognosis of esophageal squamous cell carcinoma. From January 2005 to December 2009, all the resected patients in the People's Hospital of Linzhou City, where the incidence of esophageal cancer was high, were collected. All the tissue sections were diagnosed as esophageal squamous cell carcinoma by histopathological examination. All the patients had not received any radiotherapy or chemotherapy before operation. 2. The expression of CCL26 in 197 esophageal squamous cell carcinoma tissues and adjacent normal mucosa tissues was analyzed by immunohistochemistry. 3. The data were analyzed by SPSS17.0 statistical software package. The correlation between the expression of CCL26 and the survival of esophageal squamous cell carcinoma patients was analyzed by Kaplan-Meier. The difference was statistically significant by P 0.05. Results 1. CCL26 was expressed in esophageal carcinoma tissues and adjacent normal tissues, and CCL26 was expressed in esophageal carcinoma tissues. The positive expression rate of CCL26 was 61.8%, which was significantly higher than that of the normal group (20.6%). The difference was statistically significant (P The 5-year survival rate of patients with esophageal squamous cell carcinoma was significantly lower than that of patients with negative expression of CCL26. Conclusion 1. The high expression of CCL26 may play an important role in the occurrence and development of ESCC. The expression of CCL26 in ESCC patients may be one of the clinical prognostic indicators. Detecting the expression of CCL26 may be of clinical value in the diagnosis and prognosis of ESCC. Further studies are needed on the mechanism of CL26 overexpression and its signaling pathway.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.1
本文编号：2181798
[Abstract]:BACKGROUND & OBJECTIVE Esophageal cancer is one of the most common malignant gastrointestinal cancers in the world, which is highly aggressive. Especially in China, its distribution has obvious regional characteristics, especially in the Taihang Mountains, such as Linzhou in Anyang City, Henan Province, and Huixian City adjacent to it. Esophageal squamous cell carcinoma (ESCC) is the main histological type of esophageal cancer. Epidemiological data show that smoking, alcohol abuse, unreasonable eating habits, trace element deficiency and other environmental factors. The prognosis of esophageal squamous cell carcinoma is poor. Investigation shows that the 5-year overall survival rate of esophageal squamous cell carcinoma in many countries is only about 15%, which seriously threatens the physical and mental health of human beings. Therefore, exploring and researching the oncogene, tumor suppressor gene and molecular mechanism related to the occurrence and development of esophageal cancer is more important for early detection, early diagnosis, early treatment and improving the survival rate of esophageal cancer. Molecular proteins, with molecular weights ranging from 8 kDa to 14 kDa, belong to the superfamily of small proteins. They are well known for their ability to manipulate leukocyte migration in vivo, such as eosinophils migrating to CCL11 and neutrophils migrating to CXCL 8. Chemokines bind to other homologous G protein-coupled receptors, thereby mediating a series of fine particles. Chemokines play an important role in regulating the differentiation, development and directional migration of immune cells. Chemokines are closely related to human inflammation, tumorigenesis and development. Chronic inflammation caused by long-term stimulating factors (such as bacteria, viruses, etc.) can greatly increase the probability of precancerous lesions in the body. At the same time, chemokines can induce angiogenesis, maintain tumor growth, and even help tumor cells escape immune surveillance. In short, chemokines play an important role in the development of tumor. CCL26 can also be called Eotaxin-26. 3. Macrophage inflammatory protein 4-alpha, located on chromosome 7q11.2, induces small cytokine subfamily A, member 26 (SCYA26), a member of the CC chemokine family, acting on eosinophils, T cells; receptor CCR3. Chemokine receptors and their corresponding ligands have been shown to be malignant. CCL26 plays an important role in the occurrence and development of sex tumors. CCL26 can mediate the chemotaxis of inflammatory cells and the proliferation of tumor cells. It also plays an important role in regulating the growth and metastasis of tumor cells. The expression level of CCL26 in normal esophageal mucosa adjacent to carcinoma was studied in order to understand the relationship between the expression level of CCL26 and the occurrence, development and prognosis of esophageal squamous cell carcinoma. From January 2005 to December 2009, all the resected patients in the People's Hospital of Linzhou City, where the incidence of esophageal cancer was high, were collected. All the tissue sections were diagnosed as esophageal squamous cell carcinoma by histopathological examination. All the patients had not received any radiotherapy or chemotherapy before operation. 2. The expression of CCL26 in 197 esophageal squamous cell carcinoma tissues and adjacent normal mucosa tissues was analyzed by immunohistochemistry. 3. The data were analyzed by SPSS17.0 statistical software package. The correlation between the expression of CCL26 and the survival of esophageal squamous cell carcinoma patients was analyzed by Kaplan-Meier. The difference was statistically significant by P 0.05. Results 1. CCL26 was expressed in esophageal carcinoma tissues and adjacent normal tissues, and CCL26 was expressed in esophageal carcinoma tissues. The positive expression rate of CCL26 was 61.8%, which was significantly higher than that of the normal group (20.6%). The difference was statistically significant (P The 5-year survival rate of patients with esophageal squamous cell carcinoma was significantly lower than that of patients with negative expression of CCL26. Conclusion 1. The high expression of CCL26 may play an important role in the occurrence and development of ESCC. The expression of CCL26 in ESCC patients may be one of the clinical prognostic indicators. Detecting the expression of CCL26 may be of clinical value in the diagnosis and prognosis of ESCC. Further studies are needed on the mechanism of CL26 overexpression and its signaling pathway.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.1
【参考文献】
相关期刊论文 前2条
1 崔丽焕;;白细胞介素8在肿瘤进展中的作用[J];国际免疫学杂志;2006年04期
2 屈峰;杜岳峰;邢毅飞;肖亚军;肖传国;郭宏骞;;趋化因子受体4在前列腺癌中的表达及其与转移的相关性研究[J];临床泌尿外科杂志;2008年12期
，本文编号：2181798
本文链接：https://www.wllwen.com/yixuelunwen/zlx/2181798.html
