Table 1.
Study | Levels | Study type | Characterized by | Subtypes of HB (clusters) | Features | Number of HBs |
---|---|---|---|---|---|---|
Cairo et al26 | RNA | Transcriptomic | 16-Gene signature gene expression profiling | C1, C2 | C1: enriched in hepatic perivenous program-related genes; β-catenin membranous and cytoplasmic accumulation. C2: enriched in cell-cycle and stem-cell-related genes; β-catenin nuclear accumulation. |
85 |
Cairo et al27 | miRNA | Transcriptomic/epigenetic variation | 4-miR signature miRNA expression profiling | Cm1, Cm2 | Cm1:miR-100/let-7a-2/miR-125b-1 cluster overexpression Cm2: miR-371–3 cluster overexpression |
65 |
Hooks et al28 | RNA | Transcriptomic | 4-Gene signature gene expression profiling | C1, C2A, and C2B | C1: stronger diffused ITGA6 staining. C2A: upregulation of TOP2A, FA pathway activation. C2B: VIM organized into visible spindle-shaped structures. |
39 |
Carrillo-Reixach et al29 | DNA | Epigenetic variation | DNA hypomethylation and CpG island hypermethylation | Epi-CA and Epi-CB | Epi-CA: a weak global hypomethylation except for CpG islands compared with Epi-CB. Epi-CB: activation of Wnt/β- catenin signaling and a strong 14q32-gene signature. | 113a |
Sumazin et al30 | DNA, RNA | Genomic and transcriptomic | Differential activation of hepatic progenitor cell markers and metabolic pathways | HB1, HB2, and HB3 | HB1 (low risk): low expression of LIN28B and let-7; high expression of HNF1A. HB2 (high risk): high expression of NFE2L2, LIN28B, HMGA2, SALL4, AFP, oncofetal proteins and stem-cell markers. HB3 (intermediate-risk): situated between HB1 and HB2. |
88 |
Abbreviations: AFP, α-fetoprotein; HMGA2, high mobility group AT-hook 2; HNF1A, hepatic nuclear factor 1 α; ITGA6, integrin α 6; let-7, lethal-7; LIN28B, lin-28 homolog B; NFE2L2, nuclear factor, erythroid 2–like 2; SALL4, spalt-like transcription factor 4; TOP2A, topoisomerase 2-α.
113 HBs (discovery set: 33 patients; validation set: 80 patients).