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骨桥蛋白在鼻咽癌组织中的表达及临床意义

发布时间:2018-11-08 13:37
【摘要】: 背景:鼻咽癌(nasopharyngeal carcinoma, NPC)是一种原发于鼻咽部的恶性肿瘤,它的病因、发生、发展及治疗等在诸方面均与其他头颈肿瘤有极大地不同。NPC在中国的南方地区比其他地区更为常见。它的发病机制是一个复杂的过程,主要涉及到遗传易感性、EB病毒感染和环境因素等,但是很多具体机制还不清楚。骨桥蛋白(osteopontin, OPN)是一种重要的多功能细胞外基质磷酸化糖蛋白。近来,研究表明OPN在多种肿瘤中都过度表达,包括肺癌、乳腺癌、结肠直肠癌、胃癌、卵巢癌、黑色素瘤和间皮瘤等。OPN通过与广泛分布在细胞表面上的受体相互作用,参与多种癌的许多生理和病理过程,主要涉及肿瘤的恶性转化、浸润、转移和发展等。甚至有人提出OPN可以作为肿瘤分子靶向治疗的一个靶点。目前,OPN在NPC组织的表达情况及其意义尚有待于阐明。 目的:研究OPN在NPC组织标本中表达情况并且探讨其在NPC中的意义;为NPC的早期诊断和临床治疗提供参考指标和理论基础。 试验设计、材料和方法:用横向调查的方法对NPC、慢性鼻咽炎组织和癌旁非癌组织进行研究。用半定量逆转录多聚酶链式反应(RT-PCR)的方法测定OPN mRNA在新鲜的冰冻组织中的相对表达,mRNA的含量用图像分析技术来定量;用免疫组织化学法(IHC)对石蜡包埋的组织切片中OPN的表达的程度、强度和定位进行评估。统计分析OPN mRNA和OPN蛋白的表达和NPC患者临床参数之间的关系。我们还用蛋白印迹法(WB)检测了12对NPC癌组织和癌旁非癌组织的配对标本中OPN蛋白的表达情况。 结果:从半定量RT-PCR的结果中我们得到OPN/GAPDH(mRNA灰度值)的均数(±标准差)在44例NPC组织中为0.80(±0.24),相比之下15例慢性炎症组织中仅为0.32(±0.18),二组之间有统计学意义(P0.05)。IHC染色显示OPN蛋白主要定位于肿瘤细胞的细胞浆中,其阳性表达率在67例NPC组织中(88.1%%)显著高于21例慢性鼻咽炎组织中的阳性率(28.6%)(P0.05)。对以上两个结果统计学分析显示OPN mRNA和OPN蛋白的表达均和年龄和性别无关(P0.05),与肿瘤的T、N和临床分期有关(P0.05)。WB结果显示OPN蛋白的表达水平在癌组织中高于相对应的癌旁非癌组织中的表达,平均OPN/β-Actin(灰度值)分别为0.83(±0.16)和0.51(±0.21),二组有显著差异(P0.05)。 结论:我们的研究结果表明OPN mRNA和OPN蛋白在NPC组织中过度表达,推测它可能参与了NPC的恶性转化;OPN mRNA和OPN蛋白的表达和NPC的临床参数密切相关,推测它在NPC的侵袭、转移和进展中起到某种作用。
[Abstract]:Background: nasopharyngeal carcinoma (nasopharyngeal carcinoma, NPC) is a primary malignant tumor in the nasopharynx. Development and treatment are significantly different from other head and neck tumors. NPC is more common in southern China than in other regions. Its pathogenesis is a complex process, mainly involving genetic susceptibility, EB virus infection and environmental factors, but many specific mechanisms are not clear. Osteopontin (osteopontin, OPN) is an important multifunctional extracellular matrix phosphorylated glycoprotein. Recently, studies have shown that OPN is overexpressed in a variety of tumors, including lung cancer, breast cancer, colorectal cancer, gastric cancer, ovarian cancer, melanoma and mesothelioma. OPN interacts with receptors widely distributed on the cell surface. Participate in many physiological and pathological processes of cancer, mainly involved in malignant transformation, invasion, metastasis and development. It has even been suggested that OPN can be used as a target for tumor molecular targeting therapy. At present, the expression of OPN in NPC and its significance need to be clarified. Objective: to study the expression of OPN in NPC tissues and its significance in NPC, and to provide a reference index and theoretical basis for the early diagnosis and clinical treatment of NPC. Design, materials and methods: NPC, chronic nasopharyngitis and adjacent non-cancerous tissues were studied by transverse survey. The relative expression of OPN mRNA in fresh frozen tissues was determined by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and the content of mRNA was quantified by image analysis. The degree, intensity and localization of OPN expression in paraffin embedded tissue sections were evaluated by immunohistochemical (IHC). The relationship between the expression of OPN mRNA and OPN protein and the clinical parameters of NPC patients was analyzed statistically. We also detected the expression of OPN protein in 12 pairs of matched specimens of NPC and non-cancerous adjacent tissues by Western blot (WB). Results: from the results of semi-quantitative RT-PCR, we obtained that the mean value of OPN/GAPDH (卤standard deviation) was 0.80 (卤0.24) in 44 cases of NPC, compared with 0.32 (卤0.18) in 15 cases of chronic inflammation. There was significant difference between the two groups (P0.05). IHC staining showed that OPN protein was mainly located in the cytoplasm of tumor cells. The positive expression rate in 67 cases of NPC (88.1%) was significantly higher than that of 21 cases of chronic nasopharyngitis (28.6%) (P0.05). Statistical analysis of the above two results showed that the expression of OPN mRNA and OPN protein was not related to age and sex (P0.05), but related to tumor T, N was correlated with clinical stage (P0.05). WB results showed that the expression of OPN protein in cancer tissues was higher than that in adjacent non-cancerous tissues. The average OPN/ 尾-Actin (gray value) was 0. 83 (卤0. 16) and 0. 51 (卤0. 21), respectively. There was significant difference between the two groups (P0.05). Conclusion: our results suggest that OPN mRNA and OPN proteins are overexpressed in NPC tissues and may be involved in the malignant transformation of NPC. The expression of OPN mRNA and OPN proteins is closely related to the clinical parameters of NPC. It is assumed that they play a role in the invasion, metastasis and progression of NPC.
【学位授予单位】:中南大学
【学位级别】:硕士
【学位授予年份】:2010
【分类号】:R739.63

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相关期刊论文 前2条

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2 张永钢,韩梅,温进坤;骨桥蛋白的病理功能[J];中国老年学杂志;2005年02期



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