Novel endothelial cell markers in hepatocellular carcinoma
Novel endothelial cell markers in hepatocellular carcinoma
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DOI：
10.1038/modpathol.3800167
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发表时间：
2004-10-01
期刊：
影响因子：
7.5
通讯作者：
So, S
中科院分区：
文献类型：
--
作者：
Chen, X;Higgins, J;So, S
肝细胞癌的特点是血管丰富和血管浸润的倾向。详细分析互补DNA（cDNA）微阵列的全球基因表达数据，并进一步验证一个较小的独立样本集的逆转录聚合酶链反应建立了两个内皮细胞基因簇在肝细胞癌的存在。簇I由20个cDNA克隆组成，代表15个独特的基因。簇II由9个独特的基因组成。与正常肝、肝硬化肝或邻近肝细胞癌的非肿瘤肝组织相比，肝细胞癌中I类基因的表达明显上调。第一组基因的基因表达模式与“增殖基因组”和“基质细胞组2”呈正相关。相比之下，簇II基因的表达在肝细胞癌和非肿瘤性肝组织之间没有显著差异。通过免疫组织化学染色的组织阵列与多达350个核心的组织，并通过原位杂交进行本地化这些基因的蛋白质产物的研究，导致发现新的肝细胞癌窦内皮细胞标志物：podocalyxin-like和G蛋白信号转导调节因子-5。我们的研究结果不仅强调了肿瘤与非肿瘤肝细胞之间的根本差异，而且还强调了肝细胞癌和正常肝脏的肝窦内皮之间的根本差异。
Hepatocellular carcinoma is characterized by hypervascularity and a propensity for vascular invasion. Detailed analysis of complementary DNA (cDNA) microarray global gene expression data and further validation on a smaller independent sample set by reverse transcription-polymerase chain reaction established the presence of two endothelial gene clusters in hepatocellular carcinoma. Cluster I, consists of 20 cDNA clones, representing 15 unique genes. Cluster II consists of nine unique genes. The expression of the cluster I genes appeared to be significantly upregulated in hepatocellular carcinoma compared with normal liver, cirrhotic liver, or nontumor liver tissues adjacent to the hepatocellular carcinoma. The pattern of gene expression of cluster I genes correlated positively with the 'proliferation gene cluster' and 'stromal cells cluster 2'. Expression of cluster II genes, in contrast, was not significantly different between hepatocellular carcinoma and non-neoplastic liver tissues. Studies conducted to localize the protein products of these genes by immunohistochemical staining of tissue arrays with up to 350 cores of tissues, and by in situ hybridization led to the discovery of novel sinusoidal endothelial cell markers in hepatocellular carcinoma: podocalyxin-like and regulator of G protein signaling-5. Our results underscore fundamental differences not only between neoplastic vs non-neoplastic liver cells but also between the hepatic sinusoidal endothelium of hepatocellular carcinoma and normal liver.