非小细胞肺癌中Biglycan高表达与肺癌的恶性程度相关

Up- regulation of Biglycan is Associated with Malignant Phenotype of Nonsmall Cell Lung Cancer

目的研究Biglycan在人非小细胞肺癌中的表达，并分析其表达与肺癌临床病理特征及恶性程度的关系。方法采用免疫组织化学（sP）法检测102例非小细胞肺癌石蜡包埋组织中Biglycan蛋白的表达情况，分析其表达与临床病理因素之间的相关性。应用Western blot法及RT—PCR方法检测肺癌细胞中Biglycan的表达情况，采用脂质体介导法将Biglycan干扰片段Biglycan siRNA转染入肺癌细胞系A549和SK—MES-1后，利用RT—PCR和Westernblot法检测Biglycan在mRNA和蛋白水平的表达情况，并应用MTT法、Transwell法检测干扰Biglycan表达后对肺癌细胞增殖和侵袭的影响。结果Biglycan在非小细胞肺癌中高表达，其高表达与肺癌高TNM分期（P=0．022）、低分化（P=0．034）和淋巴结转移（P=0．028）显著相关。Biglycan在肺癌细胞系中呈高表达。在干扰Biglycan表达后，与未处理组及转染对照片段control siRNA组相比，Biglycan的mRNA（P〈0．05）和蛋白（P〈0．05）表达均明显下降，细胞生长增殖能力[P〈0．01（2～4天）；P〈0．01（2～4天）]减弱，细胞侵袭数目（8．41±1．03，11．24±1．21，P〈0．05）减少。结论非小细胞肺癌中Biglycan存在普遍高表达现象，并且Biglycan的高表达可能参与了肺癌恶性表型的形成过程。

Objective To study the expression and significance of Biglycan in the malignant progression of nonsmall cell lung cancer （NSCLC）. Methods Immunohistochemistry SP method was used to examine the expression of Biglycan protein in 102 paraffin - embeded specimens. The relationship between the expression of Biglycan protein and clinicopathological factors was analyzed. The expression of Biglycan mRNA and protein were detected by RT - PCR and Western blot. A549 and SK - MES - 1 cells were transfected with Biglycan siRNA or control siRNA using Lipofectamine 2000. The cell proliferation was analyzed by MTT and the cell invasion was tested by Tran- swell. Results Immunohistochemical analysis showed that Biglycan expression level was significantly higher in NSCLC tissues, and increased Biglycan expression in NSCLC tissues was related to poor differentiation（ P = 0. 034）, the higher clinical stage （ P = 0. 022 ） and lymph node metastasis（P = 0. 028）. The expression of Biglycan was higher in lung cancer cells than in normal bronchial epithelial cell （P 〈0. 05）. Compared with untreated and the cells transfected with control siRNA, the level of Biglycan mRNA （ P 〈 0.05 ） and protein （P 〈 0.05） were decreased in the cells transfected with the Biglycan siRNA. The cell growth rate [ P 〈0. 01 （day 2 -4） ; P 〈 0. 01 （day 2 -4） ]was slower, the numbers of cell invasion （8.41 ± 1.03,11.24 ± 1.21 ,P 〈0.05）were decreased. Conclusion Up -regulation of Biglycan is associated with malignant phenotype of human NSCLC.