Human Gene Set: DESERT_STEM_CELL_HEPATOCELLULAR_CARCINOMA_SUBCLASS_UP


Standard name DESERT_STEM_CELL_HEPATOCELLULAR_CARCINOMA_SUBCLASS_UP
Systematic name M34034
Brief description Genes up-regulated in the stem cell-type subclass of hepatocellular carcinomas. Sets created as part of a metaanalysis of nine public transcriptomic datasets merged into a metadataset including 1133 human hepatocellular carcinomas obtained after curative resection. For platform descriptions of each one of the 9 datasets, see Figure 1B in Désert et al., Hepatology (2017), 66: 1502-1518.
Full description or abstract Hepatocellular carcinomas (HCCs) exhibit a diversity of molecular phenotypes, raising major challenges in clinical management. HCCs detected by surveillance programs at an early stage are candidates for potentially curative therapies (local ablation, resection or transplantation). In the long term, transplantation provides the lowest recurrence rates. Treatment allocation is based on tumor number, size, vascular invasion, performance status, functional liver reserve and on the prediction of early (< 2 years) recurrence, which reflects the intrinsic aggressiveness of the tumor. Well-differentiated, potentially low-aggressiveness tumors form the heterogeneous molecular class of non-proliferative HCCs, characterized by an approximate 50% beta-catenin (CTNNB1) mutation rate. To define the clinical, pathological, molecular features and the outcome of non-proliferative HCCs, we constructed an 1133-HCC transcriptomic metadata set and validated findings in a publically available 210-HCC RNAseq set. We show that non-proliferative HCCs preserve the zonation program that distributes metabolic functions along the porto-central axis in normal liver. More precisely, we identified two well-differentiated, non-proliferation subclasses, namely Periportal-type (wild-type CTNNB1) and Perivenous-type (mutant CTNNB1), which expressed negatively correlated gene networks. The new Periportal-type subclass represented 29% of all HCCs; expressed an HNF4A-driven gene network, which was down-regulated in mouse Hnf4a-KO mice; were early-stage tumors by BCLC, CLIP and TNM staging systems; had no macrovascular invasion and showed the lowest metastasis-specific gene expression levels and TP53 mutation rates. Also, we identified an 8-gene Periportal-type HCC signature, which was independently associated with the highest 2-year recurrence-free survival by multivariate analyses in two independent cohorts of 247 and 210 patients. Conclusion: Well-differentiated HCCs display mutually exclusive periportal or perivenous zonation programs. Among all HCCs, Periportal-type tumors have the lowest intrinsic potential for early recurrence after curative resection.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 28498607   Authors: Désert R,Rohart F,Canal F,Sicard M,Desille M,Renaud S,Turlin B,Bellaud P,Perret C,Clément B,Lê Cao KA,Musso O
Exact source Fig. 1B & Supplemental Table 2.
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Source species Homo sapiens
Contributed by Orlando Musso (INSERM (Institut National de la Santé et de la Recherche Médicale), France.)
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