【作者】 周银杰；

【导师】 田辉；

【作者基本信息】 山东大学 ， 胸外科学， 2008， 硕士

【摘要】 目的:肿瘤的侵袭和转移是恶性肿瘤死亡的主要原因之一,但肿瘤侵袭和转移的途径和机制尚有许多不明之处有待探讨。乙酰肝素酶(heparanase,HPSE)是1999年Vlodavsky等克隆出来的一种内糖苷酶,可降解细胞外基质和基底膜中的硫酸乙酰肝素(heparansulfate,HS)。最近研究发现,HPSE在多种人类恶性肿瘤中高度表达,具有促进肿瘤细胞侵袭和转移的重要作用,并且与肿瘤新生血管的形成具有密切关系。肺癌是最常见的恶性肿瘤之一,HPSE的表达是否与肺癌的侵袭性生长和转移有关,尚未见报道。本研究通过免疫组织化学SABC法(streptavi Biotin-peroxidase complex),对一组肺癌标本HPSE蛋白表达进行检测,并结合肺癌临床病理学特征及预后进行分析,目的是:(1)探讨HPSE蛋白表达与肺癌发生、发展的关系,从而为肺癌复杂发病机理的阐明提供有意义的资料;(2)通过分析HPSE蛋白表达与肺癌临床病理学特征及预后的关系,试图寻找新的对临床有价值的肿瘤标记物,为肺癌的诊断和预后判断提供依据;(3)通过蛋白水平的研究,积累一定的经验,为进一步开展基因诊断和治疗以及抗癌药物的筛选等方面的研究探索,打下一定的基础。方法:应用免疫组化SABC法检测HPSE在65例肺癌组织中的表达,并与癌旁组织和正常肺组织对比,同时结合肺癌的临床病理学特征及预后进行分析。结果:免疫组化SABC法研究结果表明,肺癌组织中HPSE蛋白阳性表达率(50.8%)明显高于正常肺组织(4.6%)和癌旁组织(9.2%)(P＜0.05);不同病理类型肺癌组织中HPSE蛋白阳性表达率(48.4%、52.0%、66.7%、50.0%)均无显著性差异(P＞0.05);不同分化程度肺癌组织中HPSE蛋白阳性表达率(47.1%、47.8%、56.3%、55.6%)亦均无显著性差异(P＞0.05);Ⅲ期和Ⅳ期肺癌组织中HPSE蛋白阳性表达率(95.5%)明显高于Ⅰ期和Ⅱ期(27.9%和37.2%)(P＜0.05);生存3年以下的肺癌组织中HPSE蛋白阳性表达率(88.0%)明显高于生存3年以上者(27.8%)(P＜0.05)。结论:HPSE蛋白的表达在肺癌发生、发展中发挥着一定作用;肺癌的发生、发展可能与HPSE促血管生成作用密切相关;HPSE可作为判断肺癌生物学行为和患者预后的一个参考指标。更多还原

【Abstract】 OBJECTIVE: Recent researcheres have demonstrated that multiple gene changes result in tumor genesis and progression. In the complicated courses, many genes are involved, including activation of proto-oncogenes and inactivation of antioncogenes. In clinical tumor therapy , the major factor which influences patients’prognosis is the conditions of tumor invasiveness and metastasis, and tumor biological behavior is also a major element in determination of tumor therapy plan. Many tumor experts have always been working hard at the early diagnosis of tumor invasiveness and metastasis, In order to improve tumor prognosis and prolong patients’life as much as possible. Therefore, tumor markers which can provide information on the conditions of tumor invasiveness and metastasis have always been emphasized by many tumor experts and become a hot researching subject, among which is HPSE. Heparanase (HPSE) is a type of Heparin lyase which was cloned by Vlodavsky in 1991 and able to degrade the heparanase of the extracellular matrix and basement membrane. The recent research shows that HPSE is expressed highly in the malignant tumor which plays an important role in facilitating the invasion and metastasis of tumor and has a close relationship with the tumorigenesis as well. Lung cancer is the most usually malignant tumor. Whether the expression of HPSE gene relate to the invasive growth and lymph node metastasis of the lung cancer are not reported. The research tested expression of HPSE genes of 65 cases in lung cancer tissues, adjacent tissues of cancer and normal lung tissues by immunohistochemical staining so as to investigate their relationships. METHODS: The expression of HPSE protein in 65 cases of lung cancer, adjacent tissues of cancer and normal tissues was tested by immunohistochemical SABC method and analysed by clinico-pathological characteristics and prognosis of lung cancer.RESULTS: The results of immunohistochemical SABC method are that the rate of expression of HPSE in tumor tissues (50.8%) was significantly higher than that in adjacent tissues of cancer (9.2%) and normal tissues (4.6%) (P<0.05); It was shown that HPSE expression did significantly not correlate with the type(48.4%、52.0%、66.7%、50.0%)(P>0.05) and grade of the tumor (47.1%、47.8%、56.3%、55.6%) (P<0.05); but it correlated with the clinical stage (95.5%) (P<0.05) and survival time of the patients (88.0%) (P<0.05).CONCLUSIONS: The results suggested that there be overexpression of HPSE in lung cancer tissues, and which perhaps participate in regulation of tumorigenesis , progression in lung cancer . The expression of HPSE protein be used as an useful marker of the biological behavior of lung cancer and as an independent prognosis factor for the patients with lung cancer.更多还原