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Series GSE10186 Query DataSets for GSE10186
Status Public on Sep 08, 2009
Title Integrative Transcriptome Analysis Reveals Common Molecular Subtypes of Human Hepatocellular Carcinoma
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Hepatocellular carcinoma (HCC) is a highly heterogeneous disease, and prior attempts to develop genomic-based classification for HCC have yielded highly divergent results, indicating difficulty in identifying unified molecular anatomy. We performed a meta-analysis of gene expression profiles in data sets from eight independent patient cohorts across the world. In addition, aiming to establish the real world applicability of a classification system, we profiled 118 formalin-fixed, paraffin-embedded tissues from an additional patient cohort. A total of 603 patients were analyzed, representing the major etiologies of HCC (hepatitis B and C) collected from Western and Eastern countries. We observed three robust HCC subclasses (termed S1, S2, and S3), each correlated with clinical parameters such as tumor size, extent of cellular differentiation, and serum alpha-fetoprotein levels. An analysis of the components of the signatures indicated that S1 reflected aberrant activation of the WNT signaling pathway, S2 was characterized by proliferation as well as MYC and AKT activation, and S3 was associated with hepatocyte differentiation. Functional studies indicated that the WNT pathway activation signature characteristic of S1 tumors was not simply the result of beta-catenin mutation but rather was the result of transforming growth factor-beta activation, thus representing a new mechanism of WNT pathway activation in HCC. These experiments establish the first consensus classification framework for HCC based on gene expression profiles and highlight the power of integrating multiple data sets to define a robust molecular taxonomy of the disease.
Overall design Surgically resected 118 tumor tissues from patients with hepatocellular carcinoma (HCC)
Contributor(s) Hoshida Y, Nijman S, Kobayashi M, Chan JA, Brunet J, Chiang D, Villanueva A, Newell P, Camargo A, Gupta S, Moore J, Wrobel MJ, Lerner J, Reich M, Ikeda K, Hashimoto M, Watanabe G, Gabriel S, Friedman S, Kumada H, Llovet JM, Golub TR
Citation(s) 19723656, 28644127
Submission date Jan 16, 2008
Last update date Aug 11, 2017
Contact name Yujin Hoshida
Organization name University of Texas Southwestern Medical Center
Street address 5323 Harry Hines Blvd
City Dallas
State/province TX
ZIP/Postal code 75390
Country USA
Platforms (1)
GPL5474 Human 6k Transcriptionally Informative Gene Panel for DASL
Samples (118)
GSM256425 Hepatocellular carcinoma (hcc_002)
GSM256426 Hepatocellular carcinoma (hcc_005)
GSM256427 Hepatocellular carcinoma (hcc_008)
BioProject PRJNA108343

Data table header descriptions
Sample name
Predicted subclass

Data table
Sample name Predicted subclass
hcc_001 S3
hcc_002 S1
hcc_003 FDR>=0.05
hcc_004 S3
hcc_005 S3
hcc_006 FDR>=0.05
hcc_007 S3
hcc_008 S1
hcc_009 S2
hcc_010 S2
hcc_011 S3
hcc_012 S2
hcc_013 S3
hcc_014 S3
hcc_015 FDR>=0.05
hcc_016 S2
hcc_017 S1
hcc_018 S2
hcc_019 S1
hcc_020 S3

Total number of rows: 118

Table truncated, full table size 1 Kbytes.

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE10186_RAW.tar 116.9 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

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