Abstract
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.
Highlights
Hepatocellular carcinoma (HCC) is the most common adult liver malignancy and ranks among the top five causes of cancer death in the world.[1]
CD34 is known to be strongly expressed in the sinusoidal complementary DNA (cDNA) Microarray Procedure and Data Analysis endothelial cells in HCC by immunohistochemistry (IHC) compared with nontumor liver tissues, whereas antibodies against CD31 and von Willebrand factor (vWF) only stain a small number of sinusoidal endothelial cells in HCC and at lower intensity.[18,19]
We showed that each HCC has its own distinct gene expression pattern, and HCC and nontumor tissues can be readily distinguished based on their global gene expression profiles
Summary
Hepatocellular carcinoma (HCC) is the most common adult liver malignancy and ranks among the top five causes of cancer death in the world.[1]. CDNA microarray technology has been used to study gene expression patterns in different tumor types and has provided new insight into the development and classification of these cancers These studies help to elucidate novel clinical biomarkers for early detection and prognostication.[20,21,22,23] In our previous study, we described the systematic characterization of the global gene expression patterns in human liver cancers using cDNA microarrays containing 23 000 clones, representing approximately 17 600 genes.[24,25] We showed that each HCC has its own distinct gene expression pattern, and HCC and nontumor tissues can be readily distinguished based on their global gene expression profiles. We report the detailed analysis and characterization of these endothelial cell markers in HCC and nontumor liver tissues
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