肝素酶在人非小细胞肺癌组织中的表达研究

Expression of heparanase in human non-small cell lung cancer

目的 探讨肝素酶 (heparanase ,Hpa)在人非小细胞肺癌组织中的表达及其与患者临床病理特征之间的关系 ,明确其对肺癌患者预后的意义。方法 采用免疫组织化学染色 (S P法 )和Westernblot检测12 2例人非小细胞肺癌石蜡包埋组织和 3 8例新鲜肺癌组织及相应癌旁正常肺组织中肝素酶的表达情况 ,并用 χ2 检验、Cox比例风险模型和生存曲线等方法分析肝素酶在肺癌组织中的表达意义。结果 肝素酶主要表达在癌细胞膜和 /或细胞浆中。免疫组织化学结果表明 :在 12 2例非小细胞肺癌组织中有 96例 ( 78.7%)呈肝素酶阳性表达 ,而癌旁正常支气管和肺泡上皮中无阳性表达。Westernblot结果亦证实肝素酶在肺癌中的表达较癌旁正常肺组织明显增高 (P =0 .0 43 )。χ2 检验显示肝素酶表达与肺癌的临床分期 (P =0 .0 2 5 )、淋巴结转移 (P =0 .0 0 2 )和血管浸润 (P =0 .0 0 0 3 )有密切关系。生存曲线分析表明肝素酶阳性表达组患者的 5年生存率明显低于阴性组 (P =0 .0 0 0 6)。但多因素分析结果显示仅肺癌的分期、淋巴结转移和血管浸润可作为影响患者预后的风险因素。结论 肝素酶在人肺癌组织中的表达较正常肺组织明显上调 ,并与肺癌的临床分期、侵袭、转移和患者的预后相关 。

Objective To study the relationship between human heparanase expression and biological factors regarding invasion, metastasis and prognosis of human non small cell lung cancer (NSCLC). Methods The expression of heparanase was assessed in 122 paraffin embedded specimens and 38 freshly taken tissues by immunohistochemical staining and Western blot. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi square test, multivariate analysis and Kaplan Meier method. Results In the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissues (78.7%, 96/122) while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissues ( P = 0.043 ). Expression of heparanase significantly correlated with TNM stage ( P =0.025), lymphatic metastasis ( P =0.002) and vascular invasion ( P =0.000 3). The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression ( P =0.000 6). In multivariate analysis, only p TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors. Conclusion Heparanase might play an important role in the development, invasion and metastasis of NSCLC. It is indicated that patients with positive heparanase expression would have a greater chance of metastasis and a poorer prognosis. However, heparanase expression is not an independent prognostic factor.