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| Status |
Public on Dec 30, 2022 |
| Title |
The transcriptional signature for Hepatocyte Growth Factor-driven invasive growth predicts poor prognosis of human hepatocellular carcinoma. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
During embryogenesis, Hepatocyte Growth Factor (HGF) elicits a distinctive morphogenetic program, the invasive growth, by the activation of MET, whose aberrant activation in cancer drives metastatic progression. Aim of this work is to define and characterize the transcriptional signature of invasive growth, and to verify its activation in human cancers. Global expression profiling was carried out on mouse liver stem/progenitor cells (MLP-29) stimulated for different times, one, six and twenty-four hours, in vitro with HGF to define the invasive growth signature. Meta-analysis of human cancer microarray data was carried out to dissect the transcriptional modules of the invasive growth that are aberrantly activated during carcinogenesis of hepatocellular carcinoma. Differential expression analysis identified 2643 regulated genes by HGF, the invasive growth signature, subdivided in 11 gene expression clusters revealing waves of time coded transcriptional regulation. Those waves have been in-silico associated with the regulative role of the transcriptional unit of Rela/Nfkbia and Fos/Jun and biological features recapitulating the physiological invasive growth phenotype observed in cell line, such as cell motility and scattering, cellular proliferation and protection from apoptosis, cytoskeletal rearangement. Genomic meta-analysis on hepatocellular carcinoma identified of a core genes set (323 gene symbols), consistently regulated between MLP-29 and human tumors and significantly associated with cancer aggressiveness and metastasis p.val < 1*10-6, HR=5.404 CI= 2.570-11.365. The invasive growth signature recapitulates the physiopatological program driven by the stimulation of HGF in normal embryonic liver cells and its activity is observed in HCC as well as in several other tumors. This signature is associated with neoplastic progression and reliably predicts human HCC disease outcome, suggesting the involvement of the invasive growth and cancer in cancer progression. These results prompt the future application of anti-met target therapies in HCC and the application of the signature for both prognostic and predictive purposes.
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| Overall design |
TimeCourse, 3 experimental points, one reference, 2 biological replicates per experiment
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| Contributor(s) |
Medico E, Isella C, Renzulli T |
| Citation missing |
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| Submission date |
Jan 09, 2013 |
| Last update date |
Dec 30, 2022 |
| Contact name |
Enzo Medico |
| E-mail(s) |
enzo.medico@ircc.it
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| Phone |
+39-011-9933234
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| Organization name |
Candiolo Cancer Institute, University of Torino
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| Department |
Oncology
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| Lab |
Laboratory of Oncogenomics
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| Street address |
Strada Prov. 142, km 3,95
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| City |
Candiolo |
| State/province |
TO |
| ZIP/Postal code |
10060 |
| Country |
Italy |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA185814 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43393_RAW.tar |
3.1 Mb |
(http)(custom) |
TAR |
| GSE43393_non_normalized.txt.gz |
1.0 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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