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CD90在人腦膠質(zhì)瘤中的表達(dá)及臨床意義

發(fā)布時(shí)間:2018-11-05 18:45
【摘要】:目的:膠質(zhì)瘤是最常見(jiàn)的顱內(nèi)腫瘤,據(jù)統(tǒng)計(jì)資料,國(guó)內(nèi)膠質(zhì)瘤占顱內(nèi)腫瘤的35.26%~60.69%(平均44.69%),居第一位。膠質(zhì)瘤呈浸潤(rùn)性生長(zhǎng),其惡性程度高、生長(zhǎng)快、易復(fù)發(fā)。一旦發(fā)現(xiàn),往往預(yù)后不佳,生存率低,嚴(yán)重威脅人類(lèi)生命健康、正常生活工作。至今依然是所有惡性腫瘤中接受綜合治理預(yù)后最差的一類(lèi)中樞神經(jīng)系統(tǒng)腫瘤。因此,迫切需要新的策略來(lái)治療惡性神經(jīng)膠質(zhì)瘤。 CD90是細(xì)胞粘附分子免疫球蛋白超家族中最小的成員。它是一個(gè)重糖基化的糖蛋白,人類(lèi)CD90的功能是目前尚未明確。目前推測(cè)其功能與細(xì)胞-細(xì)胞、細(xì)胞-細(xì)胞質(zhì)間的作用有關(guān),與細(xì)胞凋亡和轉(zhuǎn)移、炎癥、纖維化等也可能相關(guān)。表面蛋白CD90被認(rèn)為是人類(lèi)干細(xì)胞多能性的一個(gè)主要指標(biāo)。它已在許多干細(xì)胞中和腫瘤干細(xì)胞中(造血干細(xì)胞,骨髓源性間充質(zhì)干細(xì)胞,肝干細(xì)胞,以及肝腫瘤干細(xì)胞)表達(dá)。 腫瘤干細(xì)胞是少數(shù)具有干細(xì)胞性質(zhì)的細(xì)胞群體存在于腫瘤組織中,這些細(xì)胞具有自我更新能力以及多向分化潛能。腫瘤干細(xì)胞在腫瘤組織中存在極少,可促使腫瘤的發(fā)生和發(fā)展,也是腫瘤耐藥性、復(fù)發(fā)及轉(zhuǎn)移的根源。腫瘤干細(xì)胞相比正常干細(xì)胞有以下獨(dú)有特點(diǎn):無(wú)限的自我更新能力、高致瘤性、異質(zhì)性、耐藥性和轉(zhuǎn)移性。近年來(lái)有研究表明,腦膠質(zhì)瘤內(nèi)存在少部分的腫瘤干細(xì)胞,,具有神經(jīng)干細(xì)胞特性,有進(jìn)行自我更新、多向分化及體內(nèi)致瘤的潛力,是腫瘤發(fā)生、發(fā)展的根源。 本實(shí)驗(yàn)采用免疫組織化學(xué)染色方法和實(shí)時(shí)熒光定量PCR法檢測(cè)正常腦組織和不同級(jí)別的膠質(zhì)瘤中CD90的表達(dá),從而了解CD90是否能成為判斷人腦膠質(zhì)瘤惡性程度及預(yù)后的指標(biāo),為膠質(zhì)瘤治療提供新的思路。 方法:選取2013年2月至2013年10月河北醫(yī)科大學(xué)第二醫(yī)院神經(jīng)外科腦膠質(zhì)瘤患者手術(shù)中切除的癌組織56例。10例腦組織取自于因外傷或腦出血而進(jìn)行顱內(nèi)減壓術(shù)者做對(duì)照。應(yīng)用免疫組織化學(xué)(IHCSP法)和實(shí)時(shí)熒光定量PCR法(RT-PCR)分別檢測(cè)標(biāo)本中CD90的表達(dá),用統(tǒng)計(jì)軟件SPSS13.0對(duì)實(shí)驗(yàn)所得數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析。CD90在不同臨床病理類(lèi)型之間的比較用Kruskal-WallisH檢驗(yàn)。檢驗(yàn)水準(zhǔn)α0.05。 結(jié)果: 1免疫組織化學(xué)結(jié)果顯示:CD90在正常腦組織、低級(jí)別膠質(zhì)瘤和高級(jí)別膠質(zhì)瘤中的表達(dá)情況呈現(xiàn)遞增趨勢(shì)。在所有正常腦組織中,CD90均未見(jiàn)表達(dá)。在低級(jí)別膠質(zhì)瘤組,多數(shù)未見(jiàn)CD90表達(dá),少部分可見(jiàn)CD90弱表達(dá)。在高級(jí)別膠質(zhì)瘤中,CD90的表達(dá)量明顯多于低級(jí)別膠質(zhì)瘤,所有高級(jí)別膠質(zhì)瘤中均有CD90的表達(dá),并且表達(dá)水平較高。統(tǒng)計(jì)學(xué)分析顯示CD90在正常腦組織、低級(jí)別和高級(jí)別膠質(zhì)瘤中的表達(dá)差異有統(tǒng)計(jì)學(xué)意義。隨著腫瘤的惡性度增高,CD90的表達(dá)量呈升高趨勢(shì)。組間比較得出CD90在正常腦組織與低級(jí)別膠質(zhì)瘤的差異性沒(méi)有統(tǒng)計(jì)學(xué)意義。在正常腦組織與高級(jí)別膠質(zhì)瘤的差異性有統(tǒng)計(jì)學(xué)意義。在低級(jí)別膠質(zhì)瘤與高級(jí)別膠質(zhì)瘤的差異性有統(tǒng)計(jì)學(xué)意義。 2RT-PCR檢測(cè)結(jié)果顯示:CD90在正常腦組織、低級(jí)別和高級(jí)別膠質(zhì)瘤中的表達(dá)差異有統(tǒng)計(jì)學(xué)意義。隨著腫瘤的惡性度增高,CD90的表達(dá)量呈升高趨勢(shì)。組間比較得出CD90在正常腦組織與低級(jí)別膠質(zhì)瘤的差異性有統(tǒng)計(jì)學(xué)意義。在正常腦組織與高級(jí)別膠質(zhì)瘤的差異性有統(tǒng)計(jì)學(xué)意義。在低級(jí)別膠質(zhì)瘤與高級(jí)別膠質(zhì)瘤的差異性有統(tǒng)計(jì)學(xué)意義。 結(jié)論: 1在高級(jí)別膠質(zhì)瘤(WHOIII和IV級(jí))中CD90的表達(dá)水平顯著地高于低級(jí)別膠質(zhì)瘤(WHO分級(jí)I和II)和正常腦組織。 2CD90具有很高的靈敏度和特異性的標(biāo)志物,在所有被測(cè)試的高級(jí)別膠質(zhì)瘤組織中高或中的表達(dá)水平,但在低級(jí)別膠質(zhì)瘤和正常的腦組織幾乎檢測(cè)不到。 3在免疫組織化學(xué)方法中,發(fā)現(xiàn)CD90陽(yáng)性細(xì)胞在高級(jí)別膠質(zhì)瘤形成血管樣結(jié)構(gòu)。 4對(duì)比高度分化的低級(jí)別膠質(zhì)瘤,高級(jí)別膠質(zhì)瘤多為低分化的,因此更可能含有未分化的腫瘤干細(xì)胞。該實(shí)驗(yàn)中CD90在高級(jí)別膠質(zhì)瘤中的高表達(dá)水平,而在低級(jí)別膠質(zhì)瘤中的低表達(dá),提示CD90可能為神經(jīng)系統(tǒng)腫瘤干細(xì)胞的新標(biāo)記。
[Abstract]:Objective: Glioma is the most common intracranial tumor. According to statistical data, glioma accounts for 35. 26% ~ 60. 69% (average 44. 69%) of intracranial tumors. Glioma is invasive and has a high degree of malignancy, rapid growth and easy relapse. Once found, the prognosis is not good, the survival rate is low, serious threat to human life health, normal life work. So far, it is still a kind of central nervous system tumor with the worst prognosis in all malignant tumors. Therefore, there is an urgent need for new strategies to treat malignant glioma. CD90 is the smallest in the expression of immune globulin in cell adhesion molecules Member. It is a highly glycosylated glycoprotein, and human CD90 has the function of not yet Clearly, it is estimated that its function is related to cell-cell, cell-cytoplasmic interaction, apoptosis and metastasis, inflammation, fibrosis, etc. Related. Surface protein CD90 is considered to be one of multipotent human stem cells Indicators. It has been found in many stem cells and in tumor stem cells (hematopoietic stem cells, bone marrow-derived mesenchymal stem cells, liver stem cells, and liver tumor stem cells). Tumor stem cells are a few cell populations with stem cell properties in tumor tissues, and these cells have self-renewal capabilities and multiple The differentiation potential. Tumor stem cells are rare in tumor tissue, can promote the occurrence and development of tumor, also is the tumor resistance, relapse and The source of metastasis. Tumor stem cells have the following unique characteristics compared to normal stem cells: unlimited self-renewal, high tumorigenicity, heterogeneity, drug resistance In recent years, it has been shown that there are a small number of tumor stem cells in gliomas, which have the characteristics of neural stem cells, have the potential of self-renewal, multi-directional differentiation and in vivo tumorigenesis, and are tumorigenesis. The expression of CD90 in normal brain tissues and different levels of gliomas was detected by immunohistochemical staining and real-time fluorescence quantitative PCR. Methods: 56 cases of cancer tissues were selected from February 2013 to October 2013 in the second hospital of Hebei Medical University. 10 cases of brain tissue were taken from traumatic or cerebral hemorrhage. The expression of CD90 in specimens was detected by immunohistochemistry (IHCSP) and real-time fluorescence quantitative PCR (RT-PCR). Statistical analysis of the obtained data. The comparison of CD90 between different clinical and pathological types is Kruska l-WallisH test Inspection and inspection Results: 1 Immunohistochemical results showed that CD90 was in normal brain tissues, low-grade gliomas and high-grade gliomas. There is an increasing trend in expression in gliomas. In normal brain tissues, no expression was found in CD90. In the low-grade glioma group, the majority were not seen in the CD The expression of CD90 in high-grade gliomas was significantly higher than that of low-grade gliomas, and in all high-grade gliomas The expression of CD90 was expressed and the level of expression was higher. Statistical analysis showed that CD90 was in normal brain tissue, low grade and high. There was a statistically significant difference in expression in gliomas. The expression level of CD90 increased and the expression level of CD90 increased. The results showed that CD90 was in normal brain tissue. There is no statistical significance in the difference of low-grade gliomas. There was a statistically significant difference in the difference from high-grade gliomas. In low-grade gliomas The results of RT-PCR showed that CD90 was in normal brain tissue and low level. There was a statistically significant difference in the differences in the expression of non-and high-level gliomas. The degree of malignancy of CD90 increased and the expression of CD90 increased. The difference between brain tissue and low-grade gliomas was statistically significant. The difference between brain tissue and high-grade gliomas is statistically significant. At low levels Glioma Conclusions: 1 The expression level of CD90 in high-grade gliomas (WHOIII and IV) was significantly higher than that in high-grade gliomas. higher sensitivity and specificity markers than low-grade gliomas (WHO grade I and II) and normal brain tissue, high in all high-grade glioma tissues tested or moderate level of expression, but almost undetectable in low-grade gliomas and normal brain tissues. In histochemical methods, CD90 positive cells were found to form a vascular-like structure in high-grade gliomas. Gliomas, high-grade gliomas, are low-differentiated and therefore more likely to contain undifferentiated tumor stem cells. The high level of expression of CD90 in high-grade gliomas,
【學(xué)位授予單位】:河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類(lèi)號(hào)】:R739.41

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