本文關(guān)鍵詞：IGFBP-2對胰腺癌免疫抑制細(xì)胞浸潤的影響　出處：《天津醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： IGFBP-2 胰腺癌 腫瘤微環(huán)境 免疫抑制細(xì)胞 免疫逃逸

【摘要】：目的:胰腺癌作為消化系統(tǒng)惡性腫瘤,具有早診率低、進(jìn)展快、惡性程度極高、預(yù)后極差的特點(diǎn),其治療是以手術(shù)為主的綜合治療,但效果欠佳,生存率未有明顯改善。近年來研究發(fā)現(xiàn)胰島素樣生長因子結(jié)合蛋白-2(insulin like growth factor binding protein-2,IGFBP-2)在消化系統(tǒng)惡性腫瘤發(fā)生發(fā)展過程中起重要作用。因此,本文研究IGFBP-2對胰腺癌腫瘤微環(huán)境中免疫抑制細(xì)胞浸潤的影響,為探尋胰腺癌的生物治療新靶點(diǎn)提供理論依據(jù)。方法:(1)收集2014年6月到2015年10月間于天津醫(yī)科大學(xué)總醫(yī)院行手術(shù)治療的胰腺疾病患者的資料,最終得到40例完整資料,其中胰腺癌和胰腺良性疾病各20例,將其作為研究對象,根據(jù)病理結(jié)果分為胰腺癌組和非胰腺癌組。(2)應(yīng)用酶聯(lián)免疫吸附法檢測兩組研究對象術(shù)前外周血中IGFBP-2的濃度,比較兩組間差異。(3)將術(shù)后得到的病理組織處理后,運(yùn)用免疫組織化學(xué)單染的方法檢測兩組研究對象胰腺組織中IGFBP-2的表達(dá)情況進(jìn)行陽性評分,髓源性抑制細(xì)胞(myeloid-derived suppressor cell,MDSC)和調(diào)節(jié)性T細(xì)胞(regulatory cell,Treg)細(xì)胞的浸潤情況進(jìn)行計(jì)數(shù),比較兩組間差異。(4)采用免疫組織化學(xué)雙重染色的方法檢測兩組研究對象胰腺組織中CD68和CD163雙陽性表達(dá)的M2型巨噬細(xì)胞浸潤情況,比較兩組間差異。(5)在胰腺癌組,運(yùn)用Spearman等級相關(guān)分析的統(tǒng)計(jì)學(xué)方法對胰腺癌組織IGFBP-2的表達(dá)水平與MDSC、Treg及M2型巨噬細(xì)胞浸潤情況進(jìn)行分析,探討它們之間的關(guān)系。結(jié)果:(1)胰腺癌組外周血清中IGFBP-2的濃度為(2966.246±954.555)ng/ml,明顯高于非胰腺癌組(1844.040±587.169)ng/ml,差異有統(tǒng)計(jì)學(xué)意義(t=4.478,P0.05)。(2)胰腺癌組IGFBP-2表達(dá)情況在(++)和(+++)陽性表達(dá)率為95.0%(19/20),明顯高于非胰腺癌組20.0%(4/20),差異有統(tǒng)計(jì)學(xué)意義(χ2=23.018,P0.05)。(3)胰腺癌組MDSC及Treg細(xì)胞的平均浸潤數(shù)量為(34.150±12.617)和(52.650±17.264)顯著多于非胰腺癌組(8.500±5.636)和(14.500±8.370),差異有統(tǒng)計(jì)學(xué)意義(t1=8.302,P10.05;t2=8.893,P20.05)。(4)胰腺癌組M2型巨噬細(xì)胞的平均浸潤數(shù)量為(28.250±9.430)明顯多于非胰腺癌組(5.650±3.978),差異有統(tǒng)計(jì)學(xué)意義(t=9.875,P0.05)。(5)在胰腺癌組,胰腺癌組織IGFBP-2的表達(dá)與MDSC、Treg細(xì)胞及M2型巨噬細(xì)胞浸潤情況呈正相關(guān)(r1=0.851,P10.05;r2=0.872,P20.05;r3=0.855,P30.05)。結(jié)論:(1)IGFBP-2在胰腺癌患者血清及胰腺癌組織中的表達(dá)明顯高于胰腺良性疾病患者,推測其可能在胰腺癌發(fā)生過程中起重要作用,通過某種途徑影響胰腺癌的發(fā)生發(fā)展。(2)MDSC、Treg和M2型巨噬細(xì)胞三類免疫抑制細(xì)胞在胰腺癌組織中的浸潤明顯增多,作為免疫抑制細(xì)胞其可通過自身作用或者分泌免疫抑制因子介導(dǎo)機(jī)體的免疫逃逸功能,使胰腺癌細(xì)胞能夠逃避免疫清除而進(jìn)一步增殖,從而可能使胰腺癌的進(jìn)展加快、侵襲性增強(qiáng)。(3)在胰腺癌組織中,IGFBP-2表達(dá)程度的增高,可引起胰腺癌腫瘤微環(huán)境中MDSC、Treg及M2型巨噬細(xì)胞浸潤的增多,推測免疫抑制細(xì)胞在胰腺癌組織中的浸潤受IGFBP-2的調(diào)節(jié),IGFBP-2可能通過該作用介導(dǎo)機(jī)體免疫逃逸功能,從而影響胰腺癌細(xì)胞的進(jìn)一步增殖和遷移。
[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〃杈炬按騫充笌MDSC,Treg鍙?qiáng)M2鍨嬪法鍣粏鑳?yōu)娴告鼎鎯呭喌杩涜鍒嗘灒?

本文編號：1369015