 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 01, 2012 |
| Title |
Liver Regeneration Gene Signature in Hepatitis B virus (HBV)-Associated Acute Liver Failure Identified by Gene Expression Profiling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
The liver has inherent regenerative capacity via mitotic division of mature hepatocytes. However, if the hepatic loss is massive or mature hepatocyte proliferation is impaired by chronic liver injury, HSPC are activated to support liver regeneration. Access to liver tissue from 4 patients who underwent liver transplantation for hepatitis B virus (HBV)- associated acute liver failure (ALF) provided us with the opportunity to investigate the molecular mechanisms of liver regeneration in humans by means of gene expression profiling and immunohistochemistry (IHC). Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual liver specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two-well defined clusters that segregated according to the histopathological severity, i.e. massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong hepatic stem/progenitor cell (HSPC) gene signature, as also confirmed by IHC, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of cancer stem cell genes (EpCAM, CK19 and CK7), whereas the most upregulated genes in SHN were related to cellular growth and proliferation (AKR1B10, NQO1, RRM2, SFN, TOP2A, CCNB1, CDC20, ANLN and KI67). The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound healing process. Conclusion: Our data provide evidence of marked HSPC cell activation and fibrogenesis in HBV-associated ALF, which positively correlate with the extent of liver necrosis. Moreover, we detected a strong tumorigenesis gene signature in ALF, which underlines the relationship between liver regeneration and liver cancer.
|
| |
|
| Overall design |
Liver samples were obtained from explanted liver of four patients with HBV-associated acute liver failure (4-5 samples per liver) and 10 individual normal liver donors and gene expression profiling was used to establish a molecular definition of this disease.
|
| |
|
| Contributor(s) |
Nissim O, Melis M, Diaz G, Kleiner DE, Tice A, Fantola G, Zamboni F, Mishra L, Farci P |
| Citation(s) |
23185381 |
| |
| Submission date |
Jun 26, 2012 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Patrizia Farci |
| E-mail(s) |
[email protected]
|
| Phone |
301-5942325
|
| Organization name |
National Institutes of Health
|
| Department |
National Institute of Allergy and Infectious Diseases
|
| Lab |
Hepatic Pathogenesis Section-Laboratory of Infectious Diseases
|
| Street address |
50 South Drive
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892-8009 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
|
| Samples (27)
|
| GSM952514 |
normal liver from patient 20 |
| GSM952515 |
normal liver from patient 29 |
| GSM952516 |
normal liver from patient 37 |
| GSM952517 |
normal liver from patient 60 |
| GSM952518 |
normal liver from patient 62 |
| GSM952519 |
normal liver from patient 101 |
| GSM952520 |
normal liver from patient 112 |
| GSM952521 |
HBV-associated acute liver failure liver from patient 31-1 |
| GSM952522 |
HBV-associated acute liver failure liver from patient 31-2 |
| GSM952523 |
HBV-associated acute liver failure liver from patient 31-3 |
| GSM952524 |
HBV-associated acute liver failure liver from patient 31-4 |
| GSM952525 |
HBV-associated acute liver failure liver from patient 32-1 |
| GSM952526 |
HBV-associated acute liver failure liver from patient 32-2 |
| GSM952527 |
HBV-associated acute liver failure liver from patient 32-3 |
| GSM952528 |
HBV-associated acute liver failure liver from patient 32-4 |
| GSM952529 |
HBV-associated acute liver failure liver from patient 219-1 |
| GSM952530 |
HBV-associated acute liver failure liver from patient 219-2 |
| GSM952531 |
HBV-associated acute liver failure liver from patient 219-3 |
| GSM952532 |
HBV-associated acute liver failure liver from patient 219-4 |
| GSM952533 |
HBV-associated acute liver failure liver from patient 219-5 |
| GSM952534 |
HBV-associated acute liver failure liver from patient 241-1 |
| GSM952535 |
HBV-associated acute liver failure liver from patient 241-2 |
| GSM952536 |
HBV-associated acute liver failure liver from patient 241-3 |
| GSM952537 |
HBV-associated acute liver failure liver from patient 241-4 |
|
| Relations |
| BioProject |
PRJNA169397 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE38941_RAW.tar |
179.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...