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Supplementary Figure 1. Reversion of the core transcriptional programming
of HCC cells by selected drugs. In A and B, gene set enrichment analysis (GSEA)
of the induced genes (upper panels) and the repressed genes (lower panels)
from the 935-gene HCC signature in the gene expression profiles of the SNU387 and HepG2/C3A cell lines. A, GSEA from the gene profiles of SNU-387 (left
2 panels) and HepG2/C3A (right 2 panels) cells treated with DMSO or
vorinostat. B, GSEA from the gene profiles of HepG2/C3A cells treated with
DMSO or Sorafenib (left 2 panels) or Resveratrol (right 2 panels). Positive and
negative enrichment scores (ES) were determined by GSEA. DMSO, dimethyl
sulfoxide; HCC, hepatocellular carcinoma.
Supplementary Figure 2. Four-way Venn diagram comparing gene sets
included in S1, S2 and S3 HCC subtype signatures from Hoshida’s study [1] and
our core HCC signature.
Supporting the specificity of the gene signatures in both Hoshida’s study and
our study, there was almost no overlap between the S1-3 subtype signatures
and our core HCC signature. Indeed, 82% genes included in our core HCC
signature were unique while only 3%, 2% and 13% genes overlapped with the
S1, S2 and S3 signatures, respectively. In addition, most of genes that overlap
with the S3 signature were metabolism-associated genes that were shown to
be relatively up-regulated in S3-HCC, as compared to poorly differentiated HCC
of S1 and S2 subtypes [1]. However, regardless of HCC subtypes, most of these
genes remain commonly repressed when compared to the surrounding nontumor tissues, as observed in our core HCC signature. This comparison suggests
that our core signature constitutes a unique and specific fingerprint of
recurrent and common transcriptional alterations in HCC.
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.
Integrative transcriptome analysis reveals common molecular subclasses of human
hepatocellular carcinoma. Cancer Res. 2009;69(18):7385-92. PubMed PMID: 19723656.