食管鱗狀細胞癌組織中CCL26的表達及臨床意義
發(fā)布時間：2018-08-13 18:19
【摘要】：背景與目的食管癌是世界上常見的惡性消化道腫瘤之一,具有明顯的侵襲性。在我國尤為高發(fā),其分布有著明顯的區(qū)域性特征,尤其是在太行山一帶,如河南省安陽市林州以及毗鄰的輝縣市更是食管癌的高發(fā)地區(qū)。明顯的家族聚集現(xiàn)象是該地區(qū)食管癌發(fā)病的重要特征之一,這提示著食管癌的發(fā)生和基因的易感性有關。食管癌的組織學類型主要以鱗狀細胞癌(esophageal squamous cell carcinoma,ESCC)為主。流行病學資料顯示,吸煙、酗酒、不合理的飲食習慣、微量元素缺乏等環(huán)境因素和食管鱗狀細胞癌的發(fā)生發(fā)展也有著密切的關系。食管癌的預后不佳,有調(diào)查研究表明,食管鱗狀細胞癌在世界許多國家的5年總生存率大約只有15%左右,嚴重威脅著人類的身心健康。而造成其預后差、生存率低的主要原因之一就是缺乏可靠的早期檢測指標和早期個體化的治療。所以,探索研究與食管癌的發(fā)生、發(fā)展相關的癌基因、抑癌基因、分子學機制等對于食管癌的早發(fā)現(xiàn)、早診斷、早治療以及提高食管癌的生存率更加重要。趨化因子是由白細胞分泌的可溶性小分子蛋白,其分子量為8~14k Da,屬于小蛋白類的超家族,由于其在體內(nèi)可以操縱白細胞的移行而被人們熟知,比如嗜酸性粒細胞向CCL11的遷移、中性粒細胞向CXCL8的遷移等。趨化因子和與它同源的G蛋白偶聯(lián)受體相結合,從而介導一系列的細胞生物學效應,從而在調(diào)控免疫細胞的分化、發(fā)育及定向遷移等方面起到重要的作用。趨化因子與人類炎癥、腫瘤的發(fā)生、發(fā)展密切相關,長期的刺激因素(如細菌、病毒等)所導致的慢性炎癥,可以使機體發(fā)生癌前病變的幾率大大增加,進而促進腫瘤的形成。同時,趨化因子還可以通過多種方式如自分泌或旁分泌等來誘導血管的發(fā)生,維持腫瘤生長,甚至幫助腫瘤細胞逃避機體的免疫監(jiān)測等,總之,趨化因子在腫瘤發(fā)生發(fā)展過程中起著至關重要的作用。CCL26也可稱之為Eotaxin-3,又稱巨噬細胞炎性蛋白(Macrophage inflammatory protein 4-alpha),該基因位于染色體7q11.2,誘導小細胞因子亞家族A,成員26(SCYA26),是CC類趨化因子家族中的一員,作用于嗜酸性粒細胞、T細胞;受體為CCR3。趨化因子受體及其相應配體已被證明在惡性腫瘤的發(fā)生、發(fā)展中發(fā)揮重要的作用,CCL26能夠介導炎性細胞的趨化、腫瘤細胞的增殖等生理病理過程,同時在調(diào)節(jié)腫瘤細胞的生長能力和轉(zhuǎn)移能力方面也起著重要的作用。本實驗采用免疫組織化學方法檢測了趨化因子CCL26在ESCC組織和癌旁正常食管粘膜組織中的表達水平,目的在于進一步了解CCL26表達水平與食管鱗狀細胞癌的發(fā)生、發(fā)展以及預后的關系,為研究食管癌的發(fā)病、轉(zhuǎn)移、判斷預后提供新的參考資料。材料與方法1.197例ESCC組織及相應的癌旁正常黏膜組織(距離腫塊組織大于5cm)均收集自2005年1月—2009年12月期間在食管癌高發(fā)地區(qū)林州市人民醫(yī)院的手術切除患者,全部的組織切片均經(jīng)組織病理學檢測確診為食管鱗狀細胞癌,所有的患者于術前均未曾接受過任何的放、化療等治療。2.利用組織微陣列技術制作組織芯片,采用免疫組織化學法分析197例食管鱗癌組織和癌旁相應正常黏膜組織中CCL26的表達情況。3.應用SPSS17.0統(tǒng)計軟件包對數(shù)據(jù)進行統(tǒng)計分析。分類資料采用χ2檢驗,對食管鱗癌中CCL26的表達與患者性別、年齡、臨床分期、組織類型、淋巴結轉(zhuǎn)移等指標的相關性進行分析,檢驗水準為α=0.05;Kaplan-Meier分析CCL26的表達和食管鱗癌患者的生存關系,以P0.05表示差異有統(tǒng)計學意義。結果1.CCL26在食管癌組織及癌旁正常組織中均有表達,在食管癌組織中CCL26的陽性表達率為61.8%,明顯高于癌旁正常組中的表達率(20.6%),差異有統(tǒng)計學意義(P0.05)。2.CCL26的表達與淋巴結轉(zhuǎn)移有關,而與患者的性別、年齡、腫瘤細胞的分化程度和大體分型等無關(P0.05)。3.從五年生存率曲線圖可以看出,CCL26陽性表達的食管鱗狀細胞癌患者的5年生存率明顯低于CCL26陰性表達的患者。結論1.CCL26的高表達可能在ESCC的發(fā)生、發(fā)展中發(fā)揮著重要的作用。CCL26的表達與組織學類型、細胞分化程度、TNM分期等無明顯相關,而與淋巴結轉(zhuǎn)移有關。由此推斷,CCL26陽性表達的食管鱗癌可能具有更大的侵襲、轉(zhuǎn)移能力,從而可以導致5生存率的下降。2.ESCC患者CCL26的表達情況可能作為其臨床預后指標之一,檢測CCL26的表達情況對ESCC的診斷、預后有一定的臨床價值。由于CCL26發(fā)揮作用有著其復雜性,對ESCC中CCL26高表達的機制以及其信號通路還需要做進一步的研究。
[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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.1
本文編號：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.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R735.1
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，本文編號：2181798
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