IGFBP-2对胰腺癌免疫抑制细胞浸润的影响

发布时间：2018-01-02 11:34

  本文关键词：IGFBP-2对胰腺癌免疫抑制细胞浸润的影响　出处：《天津医科大学》2016年硕士论文　论文类型：学位论文

  更多相关文章： IGFBP-2 胰腺癌 肿瘤微环境 免疫抑制细胞 免疫逃逸

【摘要】：目的:胰腺癌作为消化系统恶性肿瘤,具有早诊率低、进展快、恶性程度极高、预后极差的特点,其治疗是以手术为主的综合治疗,但效果欠佳,生存率未有明显改善。近年来研究发现胰岛素样生长因子结合蛋白-2(insulin like growth factor binding protein-2,IGFBP-2)在消化系统恶性肿瘤发生发展过程中起重要作用。因此,本文研究IGFBP-2对胰腺癌肿瘤微环境中免疫抑制细胞浸润的影响,为探寻胰腺癌的生物治疗新靶点提供理论依据。方法:(1)收集2014年6月到2015年10月间于天津医科大学总医院行手术治疗的胰腺疾病患者的资料,最终得到40例完整资料,其中胰腺癌和胰腺良性疾病各20例,将其作为研究对象,根据病理结果分为胰腺癌组和非胰腺癌组。(2)应用酶联免疫吸附法检测两组研究对象术前外周血中IGFBP-2的浓度,比较两组间差异。(3)将术后得到的病理组织处理后,运用免疫组织化学单染的方法检测两组研究对象胰腺组织中IGFBP-2的表达情况进行阳性评分,髓源性抑制细胞(myeloid-derived suppressor cell,MDSC)和调节性T细胞(regulatory cell,Treg)细胞的浸润情况进行计数,比较两组间差异。(4)采用免疫组织化学双重染色的方法检测两组研究对象胰腺组织中CD68和CD163双阳性表达的M2型巨噬细胞浸润情况,比较两组间差异。(5)在胰腺癌组,运用Spearman等级相关分析的统计学方法对胰腺癌组织IGFBP-2的表达水平与MDSC、Treg及M2型巨噬细胞浸润情况进行分析,探讨它们之间的关系。结果:(1)胰腺癌组外周血清中IGFBP-2的浓度为(2966.246±954.555)ng/ml,明显高于非胰腺癌组(1844.040±587.169)ng/ml,差异有统计学意义(t=4.478,P0.05)。(2)胰腺癌组IGFBP-2表达情况在(++)和(+++)阳性表达率为95.0%(19/20),明显高于非胰腺癌组20.0%(4/20),差异有统计学意义(χ2=23.018,P0.05)。(3)胰腺癌组MDSC及Treg细胞的平均浸润数量为(34.150±12.617)和(52.650±17.264)显著多于非胰腺癌组(8.500±5.636)和(14.500±8.370),差异有统计学意义(t1=8.302,P10.05;t2=8.893,P20.05)。(4)胰腺癌组M2型巨噬细胞的平均浸润数量为(28.250±9.430)明显多于非胰腺癌组(5.650±3.978),差异有统计学意义(t=9.875,P0.05)。(5)在胰腺癌组,胰腺癌组织IGFBP-2的表达与MDSC、Treg细胞及M2型巨噬细胞浸润情况呈正相关(r1=0.851,P10.05;r2=0.872,P20.05;r3=0.855,P30.05)。结论:(1)IGFBP-2在胰腺癌患者血清及胰腺癌组织中的表达明显高于胰腺良性疾病患者,推测其可能在胰腺癌发生过程中起重要作用,通过某种途径影响胰腺癌的发生发展。(2)MDSC、Treg和M2型巨噬细胞三类免疫抑制细胞在胰腺癌组织中的浸润明显增多,作为免疫抑制细胞其可通过自身作用或者分泌免疫抑制因子介导机体的免疫逃逸功能,使胰腺癌细胞能够逃避免疫清除而进一步增殖,从而可能使胰腺癌的进展加快、侵袭性增强。(3)在胰腺癌组织中,IGFBP-2表达程度的增高,可引起胰腺癌肿瘤微环境中MDSC、Treg及M2型巨噬细胞浸润的增多,推测免疫抑制细胞在胰腺癌组织中的浸润受IGFBP-2的调节,IGFBP-2可能通过该作用介导机体免疫逃逸功能,从而影响胰腺癌细胞的进一步增殖和迁移。
[Abstract]:Objective: pancreatic cancer is the malignant tumor of digestive system, with the low rate of early diagnosis, rapid progress, high malignancy, poor prognosis features, the treatment is comprehensive treatment based on surgery, but the effect is poor, the survival rate has not improved significantly. Recent studies have found that insulin-like growth factor binding protein -2 (insulin like growth factor binding protein-2, IGFBP-2) plays an important role in the process of occurrence of malignant tumor of digestive system development. Therefore, this paper studies the IGFBP-2 of pancreatic cancer in tumor microenvironment immunosuppressive effects of cell infiltration, provide a theoretical basis for exploring the biological treatment of pancreatic cancer target. Methods: (1) from June 2014 to October 2015 in surgical treatment General Hospital Affiliated to Tianjin Medical University for pancreatic disease patients, 40 patients eventually received complete information, including pancreatic cancer and benign disease in 20 cases, as the study of Like, according to the pathological results were divided into pancreatic cancer group and non pancreatic cancer group. (2) concentration using IGFBP-2 enzyme-linked immunosorbent assay in two groups of subjects before surgery in the peripheral blood, the difference between the two groups. (3) will get the postoperative pathology after treatment, positive expression score IGFBP-2 by using the method of immunohistochemistry staining detection of two groups of pancreatic tissue, myeloid derived suppressor cells (myeloid-derived suppressor cell, MDSC) and regulatory T cells (regulatory, cell, Treg) of the number of infiltrating cells, the difference between the two groups. (4) M2 CD68 and CD163 macrophages by using the method of immunohistochemical double staining detection of two groups of double positive expression of pancreatic tissue infiltration, the difference between the two groups. (5) in pancreatic cancer group, with statistical method, Spearman rank correlation analysis of pancreatic cancer IGFBP -2鐨勮〃杈炬按骞充笌MDSC,Treg鍙奙2鍨嬪法鍣�缁嗚優娴告鼎鎯呭喌杩涜�屽垎鏋，

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