Transcription profiling of human hepatocellular carcinoma reveals common molecular subtypes

ABSTRACT: Hepatocellular carcinoma (HCC) is a common malignancy with high mortality due to a lack of effective therapies. HCC represents a collection of highly heterogeneous tumor types but a general molecular classification of HCC is lacking. Here, we define three molecular subtypes of HCC that are observed across various independent patient cohorts and profiling platforms. Analysis of the expression signatures indicates that a limited number of pathways and processes drive the clustering of these subtypes. Notably, TGF-beta signaling is a critical factor that distinguishes two subtypes of high-grade tumors, and is associated with early tumor recurrence. Furthermore, both bioinformatics and functional analyses reveal molecular crosstalk between TGF-beta and WNT signaling pathways. These findings suggest that TGF-beta plays a critical role in a subclass of HCC tumors and may enhance WNT pathway activation in the absence of activating mutations in canonical pathway components. This study is an example of how robust molecular subclassification can be used to interrogate molecular abnormalities in the context of human cancer. Experiment Overall Design: Four hepatocellular carcinoma (HCC) cell line samples treated or untreated by TGF-beta

ORGANISM(S): Homo sapiens

SUBMITTER: Yujin Hoshida 

PROVIDER: E-GEOD-10393 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress