Novel endothelial cell markers in hepatocellular carcinoma.
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.
Chen
Xin
X
Department of Biopharmaceutical Sciences, University of California San Francisco, USA.
Higgins
John
J
Cheung
Siu-Tim
ST
Li
Rui
R
Mason
Veronica
V
Montgomery
Kelli
K
Fan
Sheung-Tat
ST
van de Rijn
Matt
M
So
Samuel
S
D018952:Antigens, CD34 / Q000032:analysis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016000:Cluster Analysis; D042783:Endothelial Cells / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020710:RGS Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins; D014841:von Willebrand Factor / Q000032:analysis / Q000235:genetics
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D020710:RGS Proteins; C491349:RGS5 protein, human; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C001643:podocalyxin; D014841:von Willebrand Factor