Specific expression of osteopontin and S100A6 in hepatocellular carcinoma
Specific expression of osteopontin and S100A6 in hepatocellular carcinoma
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DOI：
10.1016/j.surg.2010.12.007
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发表时间：
2011-06-01
期刊：
影响因子：
3.8
通讯作者：
Yao, Li
中科院分区：
文献类型：
--
作者：
Hua, Zhan;Chen, Jingzhou;Yao, Li
背景我们的目的是确定差异表达的基因在肝细胞癌（HCC）的最终目标是发现新的，诊断和治疗的目标。我们使用一个含有15，843个基因/克隆的探针的cDNA阵列检测了HCC和非癌肝组织之间基因表达的差异。骨桥蛋白（OPN）和S100 A6两个基因的表达差异大于10倍，并在51例HCC和10例非恶性肝脏标本中进行了进一步的免疫组化染色。同时分析OPN和S100 A6蛋白的改变与各种临床病理参数的关系。我们发现总共有219个基因差异表达>3倍。其中，109个上调，110个下调。在这一组中，123个基因，包括59个上调和64个下调，已被确定。这些已知的基因主要涉及细胞迁移、细胞骨架动力学、信号通路和细胞周期以及代谢。OPN表达和S100 A6表达分别见于51例肝癌样本中的26例（51.0%）和51例肝癌样本中的16例（31.4%）。更重要的是，通过免疫组织化学分析，在任何非癌性肝脏标本中均未发现由这些基因编码的蛋白质。这些基因的表达与低分化相关（OPN：P = .013; S100 A6：P = .008）。骨桥蛋白是一种分泌型磷蛋白，与肿瘤的进展和转移密切相关，S100 A6是S100蛋白家族的成员，具有细胞增殖、分化、迁移和细胞骨架动力学等功能，可能成为HCC的诊断标志物和治疗靶点。此外，这些结果鼓励未来的研究，涉及这些蛋白质在这种癌症的发展和进展中的作用。（Surgery 2011;149：783-91.）
Background. Our aim was to identify differential expression of genes in hepatocellular carcinoma (HCC) with the ultimate goal of discovering novel, diagnostic and therapeutic targets.Methods. We examined differences in gene expression between HCC and noncancerous liver tissue using a cDNA array with probes for 15,843 genes/clones. Two genes, osteopontin (OPN) and S100A6, were found to be >10-fold differentially expressed, and were selected for further immunohistochemical staining in 51 HCC and 10 nonmalignant liver specimens. The relation between OPN and S100A6 alterations and various clinicopathologic parameters was also evaluated.Results. We found a total of 219 genes that were differentially expressed >3-fold. Of these, 109 were upregulated and 110 downregulated. Within this group, 123 genes, including 59 upregulated and 64 downregulated, had been identified previously. These known genes were mainly involved in cell migration, cytoskeleton dynamics, the signaling pathway and cell cycle, and metabolism. OPN expression and S100A6 expression were seen in 26 of 51 (51.0 %) and 16 of 51 (31.4 %) HCC samples, respectively. More importantly, proteins coded by these genes were not found in any noncancerous liver specimen by immunohistochemical analysis. Expression of these genes correlated with poor differentiation (OPN: P = .013; S100A6: P = .008).Conclusion. OPN, a secreted phosphoprotein that has been increasingly implicated in the progression and metastasis of cancer, and S100A6, a member of the S100 protein family that can perform cell proliferation, differentiation, migration, and cytoskeletal dynamics, may be promising diagnostic markers and therapeutic targets for HCC. In addition, the results encourage future studies involving the roles of these proteins in the development and progression of this cancer. (Surgery 2011;149:783-91.)