Transcriptomic and genomic analysis of human hepatocellular carcinomas and hepatoblastomas.
This study analyzed gene expression patterns and global genomic alterations in hepatocellular carcinomas (HCC), hepatoblastomas (HPBL), tissue adjacent to HCC and normal liver tissue derived from normal livers and hepatic resections. We found that HCC and adjacent non-neoplastic cirrhotic tissue have considerable overlap in gene expression patterns compared to normal liver. Several genes including Glypican 3, spondin-2, PEG10, EDIL3 and Osteopontin are over-expressed in HCC vs. adjacent tissue whereas Ficolin 3 is the most consistently under-expressed gene. HCC can be subdivided into three clusters based on gene expression patterns. HCC and HPBL have clearly different patterns of gene expression, with genes IGF2, Fibronectin, DLK1, TGFb1, MALAT1 and MIG6 being over-expressed in HPBL versus HCC. In addition, specific areas of the genome appear unstable in HCC, with the same regions undergoing either deletion or increased gene dosage in all HCC. In conclusion, a set of specific genes and areas of genomic instability are found across the board in liver neoplasia.
Luo
Jian-Hua
JH
Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Ren
Baoguo
B
Keryanov
Sergei
S
Tseng
George C
GC
Rao
Uma N M
UN
Monga
Satdarshan P
SP
Strom
Steven
S
Demetris
Anthony J
AJ
Nalesnik
Michael
M
Yu
Yan P
YP
Ranganathan
Sarangarajan
S
Michalopoulos
George K
GK
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis; D015815:Cell Adhesion Molecules; D016000:Cluster Analysis; D004268:DNA-Binding Proteins; D005353:Fibronectins / Q000096:biosynthesis; D005355:Fibrosis / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006023:Glycoproteins / Q000096:biosynthesis; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000096:biosynthesis; D018197:Hepatoblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis; D053495:Osteopontin; D011506:Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000096:biosynthesis; D012795:Sialoglycoproteins / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C512941:DLK1 protein, human; D004268:DNA-Binding Proteins; C110183:EDIL3 protein, human; C109662:FCN3 protein, human; D005353:Fibronectins; D006023:Glycoproteins; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; C035170:IGF2 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D008565:Membrane Proteins; C432965:PEG10 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053495:Osteopontin; D007335:Insulin-Like Growth Factor II