STANDARD_NAME COULOUARN_TEMPORAL_TGFB1_SIGNATURE_UP SYSTEMATIC_NAME M18762 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/COULOUARN_TEMPORAL_TGFB1_SIGNATURE_UP NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF 'Late-TGFB1 signature': genes overexpressed in primary hepatocytes at a late phase of TGFB1 [GeneID=7040] treatment; is associated with a more invasive phenotype. DESCRIPTION_FULL Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. The clinical heterogeneity of HCC, and the lack of good diagnostic markers and treatment strategies, has rendered the disease a major challenge. Patients with HCC have a highly variable clinical course, indicating that HCC comprises several biologically distinctive subgroups reflecting a molecular heterogeneity of the tumors. Transforming growth factor beta (TGF-beta) is known to exhibit tumor stage dependent suppressive (that is, growth inhibition) and oncogenic (that is, invasiveness) properties. Here, we asked if a TGF-beta specific gene expression signature could refine the classification and prognostic predictions for HCC patients. Applying a comparative functional genomics approach we demonstrated that a temporal TGF-beta gene expression signature established in mouse primary hepatocytes successfully discriminated distinct subgroups of HCC. The TGF-beta positive cluster included two novel homogeneous groups of HCC associated with early and late TGF-beta signatures. Kaplan-Meier plots and log-rank statistics indicated that the patients with a late TGF-beta signature showed significantly (P < 0.005) shortened mean survival time (16.2 +/- 5.3 months) compared to the patients with an early (60.7 +/- 16.1 months) TGF-beta signature. Also, tumors expressing late TGF-beta-responsive genes displayed invasive phenotype and increased tumor recurrence. We also showed that the late TGF-beta signature accurately predicted liver metastasis and discriminated HCC cell lines by degree of invasiveness. Finally, we established that the TGF-beta gene expression signature possessed a predictive value for tumors other than HCC. CONCLUSION: These data demonstrate the clinical significance of the genes embedded in TGF-beta expression signature for the molecular classification of HCC. PMID 18506891 GEOID GSE1898,GSE4024 AUTHORS Coulouarn C,Factor VM,Thorgeirsson SS CONTRIBUTOR Yujin Hoshida CONTRIBUTOR_ORG Broad Institute EXACT_SOURCE Table 2S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AFP,ALS2,ALS2CR17,AMD1,ASNS,BCL2L14,BCL3,BHLHB2,BTG1,C12orf2,C1orf42,C6orf133,C9orf72,Cep192,CLDN4,CLIC4,CPD,CSNK1E,CTGF,CXCL1,CXCL10,DDIT4,DDR1,DHX32,DNAPTP6,DUSP4,EMD,EPLIN,EXOC7,FAM34A,FCHO2,FGD6,FLJ10726,FLJ20273,FLJ20489,FOSL2,FOXQ1,FREQ,GGA3,GJA5,GNG13,GRB7,GTSE1,HMBS,HMG2L1,HSPA4,HTCD37,IDI1,IER3,IFNGR1,IKBKE,IMPACT,IQGAP1,ITGA6,KCTD3,KIAA1181,KIAA1632,LGMN,LMO7,MAL2,MAML2,MGC10233,NAB1,NET1,NFE2L2,NGFB,NRP1,PALMD,PARG1,PDCD10,PDGFA,PDLIM7,PICALM,PIGH,PIP5K2B,PLAT,PLEKHA3,PRO1310,RAGE,RPS6KC1,SERPINE1,SGK,Shax3,SKIL,SLC20A1,SLC29A1,SLC35D2,SLC40A1,SLC6A8,SMAD7,SMURF2,SOX4,SOX9,SPPL2A,SPRR3,SQLE,TBC1D1,TEX10,TFPI2,TGFBR1,TGIF,TMEPAI,TMSB4X,TMX2,TNFRSF1B,UAP1L1,UNC5B,VCIP135,VIM,ZAK,ZCCHC10 GENE_SYMBOLS AFP,ALS2,NBEAL1,AMD1,ASNS,BCL2L14,BCL3,BHLHE40,BTG1,RASSF8,CRCT1,UBR2,C9orf72,CLDN4,CLIC4,CPD,CSNK1E,CCN2,CXCL1,CXCL10,,DDIT4,DDR1,DHX32,SPATS2L,DUSP4,EMD,LIMA1,EXOC7,LPGAT1,FCHO2,FGD6,NKAPD1,RBM47,SLC48A1,FOSL2,FOXQ1,NCS1,GGA3,GJA5,GNG13,GRB7,GTSE1,HMBS,HMGXB4,HSPA4,PRUNE1,IDI1,IER3,IFNGR1,IKBKE,IMPACT,IQGAP1,ITGA6,KCTD3,ERGIC1,EPG5,LGMN,LMO7,MAL2,MAML2,TBCEL,NAB1,NET1,NFE2L2,NGF,NRP1,PALMD,ARHGAP29,PDCD10,PDGFA,PDLIM7,PICALM,PIGH,PIP4K2B,PLAT,PLEKHA3,,MOK,RPS6KC1,SERPINE1,SGK1,SKIL,SLC20A1,SLC29A1,SLC35D2,SLC40A1,SLC6A8,SMAD7,SMURF2,SOX4,SOX9,SPPL2A,SPRR3,SQLE,CHMP4C,TBC1D1,TEX10,TFPI2,TGFBR1,TGIF1,PMEPA1,TMSB4X,TMX2,TNFRSF1B,UAP1L1,UNC5B,VCPIP1,VIM,MAP3K20,ZCCHC10 FOUNDER_NAMES