Molecular and genetic markers in hepatocellular carcinoma: In silico analysis to clinical validation (current limitations and future promises)

Table 1 Molecular pathways affected in hepatocellular carcinoma and their related protein-coding genes[14,33,34] and KEGG pathways database[35]

Function	Pathways and genetic regulators
Proliferation	Wnt pathway: MYC, FGF19, APC, AXINMAPK/ERK signaling pathway: mTOR, ERK 1/2
Cell growth and angiogenesis	RTK/RAS/PI(3)K pathway: PIK3CA, VEGF, EGF, MET, KRAS, PTEN, AKT1/2, FGFR1, NF1, TSC1/2, TGF-β pathway: SMAD2/3, SMAD4
Apoptosis	TP53 signaling pathway: MDM4, MDM2, CDKN2A, RPS6KA3
Cell immortality	Telomerase production: TERT
Cell cycle progression	RB1, CCND1, CDK4, CCNE1
Cell differentiation	HNF1A
Autophagy	RAS/RAF/MEK/ERK pathway, PI3K-AKT (AKT kinase)-mTOR pathway, and Wnt/β-catenin signaling pathway: Becilin-1, ATG3, ATG5, ATG7
Inflammatory response	IL-6 stimulation: STAT3, HNF1, IL6ST, GNAS
Chromatin modifiers	BAP1, ARID1A/B, IDH1/2, SMACA4, KMT2D

Wnt: Wingless and Int-1 (combined word); FGF19: Fibroblast growth factor 19 coding gene; MAPK: Mitogen-activated protein kinase; ERK: Extracellular signal-regulated kinase; mTOR: The mechanistic target of rapamycin; VEGF: Vascular endothelial growth factor; EGF: Epidermal growth factor; KRAS: K-Ras coding gene; PTEN: Phosphatase and tensin homolog coding gene; FGFR1: Fibroblast growth factor receptor 1 coding gene; SMAD family: Signal transducers for receptors of the transforming growth factor beta coding genes; Tp53: Tumor protein P53; MDM2: E3 ubiquitin ligase to degrade p53 coding gene; RPS6KA3: Ribosomal Protein S6 Kinase A3 coding gene; TERT: Telomerase reverse transcriptase coding gene; CCND1: Cyclin D1 Coding gene; CDK4: Cyclin-dependent kinase 4; CCNE1: Cyclin E1 coding gene; HNF1A: HNF1 Homeobox A coding gene; IL: Interleukin; ATG: Autophagy Related coding gene; STAT3: Signal transducer and activator of transcription 3; GNAS: Guanine nucleotide binding protein; BAP1: BRCA1 associated protein-1; ARID1A/B: AT-rich interactive domain-containing protein 1A/B; IDH1/2: Isocitrate dehydrogenase 1/2; KMT2D: Lysine Methyltransferase 2D coding gene.