| RRC ID |
37629
|
| 著者 |
Hoshida Y, Nijman SM, Kobayashi M, Chan JA, Brunet JP, Chiang DY, Villanueva A, Newell P, Ikeda K, Hashimoto M, Watanabe G, Gabriel S, Friedman SL, Kumada H, Llovet JM, Golub TR.
|
| タイトル |
Integrative transcriptome analysis reveals common molecular subclasses of human hepatocellular carcinoma.
|
| ジャーナル |
Cancer Res
|
| Abstract |
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.
|
| 巻・号 |
69(18)
|
| ページ |
7385-92
|
| 公開日 |
2009-9-15
|
| DOI |
10.1158/0008-5472.CAN-09-1089
|
| PII |
0008-5472.CAN-09-1089
|
| PMID |
19723656
|
| PMC |
PMC3549578
|
| MeSH |
Carcinoma, Hepatocellular / classification*
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cohort Studies
Gene Expression Profiling
Humans
Liver Neoplasms / classification*
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Signal Transduction
Transforming Growth Factor beta / metabolism
Wnt Proteins / metabolism
beta Catenin / genetics
beta Catenin / metabolism
|
| IF |
9.727
|
| 引用数 |
526
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
