OPN和Syndecan-1在原发性肝癌中的表达及与临床病理参数之间的相关性

Study on the expression of Osteopontin and Syndecan-1 and their correlations with the clinical pathological characteristics of hepatocellular carcinoma by tissue microarray technique

目的:应用组织芯片技术考察骨桥蛋白(osteopontin,OPN)和Syndecan-1在原发性肝细胞癌(hepatocellular carcinoma,HCC)中的表达及与临床病理参数之间的相关性,分析两者在HCC发生发展过程中的可能机制.方法:应用S-P法对高通量肝癌组织芯片(478点阵,产品批号:OD-CT-DgLiv01-001)进行染色,检测OPN和Syndecan-1蛋白在肝癌、肝硬化和正常肝组织中的表达.结果:OPN在HCC、肝硬化和正常肝组织中的阳性率分别为73.3%,47.4%和22.2%,差异具有显著性(P<0.05,P<0.05);Syndecan-1在HCC、肝硬化和正常肝组织中的阳性率分别为19.6%,35.0%和90%,亦有显著性差异(P<0.05,P<0.01).单因素分析结果显示OPN的表达与肿瘤包膜的完整性(x^2=4.52,P<0.05),门静脉有无癌栓(x^2=4.28,P<0.05)及肿瘤的转移相关(x^2=7.21,P<0.05),与其他临床病理特征没有相关性;Syndecan-1的表达与肿瘤有无包膜(x^2=5.58,P<0.01),病理分级(x^2=4.35,P<0.01)以及肿瘤转移与否相关(x^2=3.37,P<0.05),与其他临床病理特征没有相关性.蛋白之间的相关性分析显示,OPN与Syndecan-1之间存在负相关(r=-0.439,P<0.01).结论:组织芯片是一种可高效率和高通量研究肿瘤分子病理的技术平台;HCC的发生发展与癌细胞OPN的过表达和Syndecan-1表达下调可能有关,OPN可能通过下调Syndecan-1的表达,降低肿瘤细胞之间的黏附性,从而促进肿瘤的转移.

AIM： To explore the expression of osteopontin （OPN） and syndecan-1 as well as their correlations with the clinical pathological characteristics of hepatocellular carcinoma （HCC） by tissue microarray （TMA） technique, and analyze the potential mechanisms during the development and progression of HCC. METHODS： The expression patterns of OPN and syndecan-1 proteins in HCC, liver cirrhosis （LC） and normal liver tissue （NLT） were investigated using high throughput TMA specified to HCC （478 spots, product batch No： OD-CT- DgLiv01-001） by SP method. RESULTS： The positive rate of OPN in HCC was significantly higher than that in LC or NLT （73.3% vs 47.4%, 22.2%, both P 〈 0.05）. Correspondingly, the positive rate of Syndecan-1 expression was significantly lower than that in LC or NLT （19.6% vs 35.0%, 90.0%, P 〈 0.05, P 〈 0.01）. The results of single-factor analysis showed that OPN expression was correlated with the integrality of tumor membrane （χ^2 = 4.52, P 〈 0.05）, the formation of embolus in portal vein （χ^2 = 4.28, P 〈 0.05） and metastases （χ^2= 7.21, P 〈 0.05）. Syndecan-1 expression was correlated with the integrality of tumor membrane （χ^2 = 5.58, P 〈 0.01）, metastases （χ^2 = 3.37, P 〈 0.05） and patho- logical grades （χ^2 = 4.35, P 〈 0.01）. Moreover, OPN was negatively correlated with syndecan-1 （r = -0.439, P 〈 0.01）. CONCLUSION： TMA is a high-throughput plat- form by which molecular pathology of cancer can be studied effectively. Over-expression of OPN and down-regulation of syndecan-1 may be involved in the development and progression of HCC, suggesting that OPN may decrease the adhesiveness of tumor cells and promote the metastasis by down-regulating the expression of syndecan-1.