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| Status |
Public on Jul 25, 2023 |
| Title |
Gene expression in 1133 HCCs |
| Experiment type |
Expression profiling by array
Third-party reanalysis
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| Summary |
Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular
phenotypes, raising major challenges in clinical management. HCCs detected
by surveillance programs at an early stage are candidates for potentially
curative therapies (local ablation, resection, or transplantation). In the
long term, transplantation provides the lowest recurrence rates. Treatment
allocation is based on tumor number, size, vascular invasion, performance
status, functional liver reserve, and the prediction of early (<2 years)
recurrence, which reflects the intrinsic aggressiveness of the tumor.
Well-differentiated, potentially low-aggressiveness tumors form the
heterogeneous molecular class of nonproliferative HCCs, characterized by an
approximate 50% beta-catenin mutation rate. To define the clinical,
pathological, and molecular features and the outcome of nonproliferative
HCCs, we constructed a 1,133-HCC transcriptomic metadata set and validated
findings in a publically available 210-HCC RNA sequencing set. We show that
nonproliferative HCCs preserve the zonation program that distributes
metabolic functions along the portocentral axis in normal liver. More
precisely, we identified two well-differentiated, nonproliferation
subclasses, namely periportal-type (wild-type beta-catenin) and
perivenous-type (mutant beta-catenin), which expressed negatively correlated
gene networks. The new periportal-type subclass represented 29% of all HCCs;
expressed a hepatocyte nuclear factor 4A-driven gene network, which was
down-regulated in mouse hepatocyte nuclear factor 4A knockout mice; were
early-stage tumors by Barcelona Clinic Liver Cancer, Cancer of the Liver
Italian Program, and tumor-node-metastasis staging systems; had no
macrovascular invasion; and showed the lowest metastasis-specific gene
expression levels and TP53 mutation rates. Also, we identified an eight-gene
periportal-type HCC signature, which was independently associated with the
highest 2-year recurrence-free survival by multivariate analyses in two
independent cohorts of 247 and 210 patients. CONCLUSION: Well-differentiated
HCCs display mutually exclusive periportal or perivenous zonation programs.
Among all HCCs, periportal-type tumors have the lowest intrinsic potential
for early recurrence after curative resection. (Hepatology
2017;66:1502-1518).
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| Overall design |
Raw feature data from Gene Expression Omnibus (GSE16757, GSE20017, GSE14520, GSE25097, GSE17856, GSE54236, GSE20140 (subSeries GSE19977, subSeries GSE56140), GSE15765) were normalized and log 2 intensity expression summary values for each probe set were calculated using Robust Multiarray Average (RMA, packages Affy or Limma). Each dataset was assessed for the detection of outliers and inter-array, experiment-related batch effects by principal component analysis (PCA) and density plots. The outliers removed were: one sample from GSE17856, one sample from GSE15765 and two samples from GSE54236. When clear-cut inter-array experiment-related batch effects were observed within a dataset, this effect was corrected by the COMBAT method (package sva). GSE25097 was corrected for 2-batch effect and GSE14520 for 3-batch effect. Then, probes being detected over the background noise in at least one HCC were retained and quantile normalized (package preprocessCore). When raw data were not available, normalized data were directly used. The final metadata set include 1,133 HCCs and 9,542 genes.
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| Contributor(s) |
Musso O, Désert R, Desquilles L, Foucher F |
| Citation(s) |
36999534, 35115564, 34730871, 30837223, 28498607 |
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| Submission date |
Jul 21, 2023 |
| Last update date |
Jul 28, 2023 |
| Contact name |
Musso Orlando |
| Organization name |
UMR-1317 INSERM - INRAe - Université de Rennes
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| Lab |
Institut NuMeCan Nutrition, Métabolismes et Cancer Bâtiment 7 – Bureau 111 Hôpital Pontchaillou
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| Street address |
rue Henri Le Guilloux
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| City |
RENNES CEDEX 9 |
| State/province |
FRANCE |
| ZIP/Postal code |
35033 |
| Country |
France |
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| Relations |
| Reanalysis of |
GSE14520 |
| Reanalysis of |
GSE15765 |
| Reanalysis of |
GSE16757 |
| Reanalysis of |
GSE17856 |
| Reanalysis of |
GSE19977 |
| Reanalysis of |
GSE20017 |
| Reanalysis of |
GSE25097 |
| Reanalysis of |
GSE54236 |
| Reanalysis of |
GSE56140 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE237977_RMAsignals_matrix.txt.gz |
54.7 Mb |
(ftp)(http) |
TXT |
| GSE237977_list_of_re-analyzed_Samples.txt.gz |
27.9 Kb |
(ftp)(http) |
TXT |
| Processed data are available on Series record |
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