Recent progress in molecular mechanisms of postoperative recurrence and metastasis of hepatocellular carcinoma

Table 1 Molecular mechanisms associated with postoperative hepatocellular carcinoma metastasis and recurrence in this review

Molecular marker	Association with HCC metastasis and recurrence	Ref.
Oncogenes and tumor suppressors
Oncogens
H-ras	Increased expression	Ma et al[9]
OPN	Increased expression	Yu et al[22]; Zhu et al[25]
S100A9	Increased expression	Chiou and Lee[29]; Liao et al[31]
Tumor suppressors
Mutated p53	Increased expression	Nikolova et al[40]; Chaudhary et al[44]
Nm23	Decreased expression	Khera et al[50]
KAI1	Decreased or lost expression	Xu et al[55]
Tumor microenvironment
Tumor stromal cells
Immune cells
T lymphocytes	Decreased expression	Cai et al[68]; Gabrielson et al[70]; Li et al[71]
NK cells	Decreased expression	Wu et al[85]; Lee et al[90]
DCs	Decreased expression	Shi et al[108]
M2-TAMs	Increased expression	Yao et al[128]; Park et al[133]; Liao et al[134]
MDSCs	Increased expression	Kalathil and Thanavala[143]; Lu et al[147]
Tregs	Increased expression	Xiong et al[155]; Trehanpati and Vyas[159]
N2-TANs	Increased expression	Zhou et al[172]; Yang et al[175]
HSCs	Increased expression	Barry et al[198]; Cheng et al[200]
CAFs	Increased expression	Gao et al[217]; Zhang et al[220]
TECs	Increased expression	Tahmasebi et al[236]; Dong et al[239]
ECM
Adhesion enhancement in tumor cell-ECM
ICAM-1	Increased expression	Chen et al[255]
E-Cadherin	Decreased or lost expression	Ren et al[267]; He et al[269]
Integrins
Oncogenic integrins	Increased expression	Zhang et al[276]; Huang et al[279]
Tumor-suppressive integrins	Decreased expression	Zhang et al[282]
Selectins
P-selectin	Increased expression	Xu et al[288]
CD44V6	Increased expression	Chen et al[292]
ECM degradation
uPA	Increased expression	Song et al[293]
MMP-2 and MMP-9	Increased expression	Liu et al[296]; Fu et al[297]
Cytokines
IFN-γ	Decreased expression	Li et al[302]
Interleukin
IL-6	Increased expression	Jiang et al[315]
IL-8	Increased expression	Zhang et al[327]
IL-1β	Increased expression	Duan et al[332]
TNF-α	Increased expression	Hammam et al[338]
Chemokines
CCL2/CCR2 axis	Increased expression	Avila and Berasain[348]
CXCL12-CXCR4 axis	Increased expression	Li et al[355]
Growth factors
VEGF	Increased expression	Zhang et al[365]
TGF-β	Increased expression	Sun et al[375]
Exosomes	Increased expression	Watanabe and Tanaka[385]; Luo et al[404]
EMT
E-cadherin	Decreased or lost expression	Xu et al[413]; Helal et al[417]
N-cadherin and Vimentin	Increased expression	Xu et al[413]; Helal et al[417]
LCSCs
CD133	Increased expression	Liu et al[363]
EpCAM	Increased expression	Tsuchiya et al[435]; Krause et al[437]
CD90	Increased expression	Yamashita and Kaneko[440]; Hwang et al[441]
CTCs	Increased expression	Schulze et al[463]
Epigenetic modifications
DNA methylation
Tumor suppressors	Hypermethylation	He et al[476]; Qian et al[478]
Oncogenes	Hypomethylation	Zhou et al[479]; Chen et al[480]
Noncoding RNAs
LncRNAs
Oncogenic lncRNAs	Increased expression	Shi et al[484]
Tumor-suppressive lncRNAs	Decreased expression	Song and Qiu[486]
CircRNAs
Oncogenic circRNAs	Increased expression	Gu et al[499]
Tumor-suppressive circRNAs	Decreased expression	Sun et al[501]
miRNAs
Tumor-suppressive miRNAs	Decreased expression	Yao et al[508]
Oncogenic miRNAs	Increased expression	Wang et al[510]

HCC: Hepatocellular carcinoma; OPN: Osteopontin; NK: Natural killer; DCs: Dendritic cells; TAMs: Tumor associated macrophages; MDSCs: Myeloid-derived suppressor cells; Tregs: T regulatory cells; TANs: Tumor-associated neutrophils; HSCs: Hepatic stellate cells; CAFs: Cancer-associated fibroblasts; TECs: Tumor-associated endothelial cells; ECM: Extracellular matrix; ICAM-1: Intercellular adhesion molecule-1; MMP-2: Matrix metalloproteinase 2; MMP-9: Matrix metalloproteinase 9; uPA: Urokinase-type plasminogen activator; IL-6: Interleukin-6; IL-8: Interleukin-8; CCL2/CCR2: Chemokine ligand 2/Chemokine receptor 2; CXCL12-CXCR4: Chemokine (C-X-C motif) ligand 12/Chemokine (C-X-C motif) receptor 4; VEGF: Vascular endothelial growth factor; TGF-β:Transforming growth factor-β; EMT: Epithelial-mesenchymal transition; LCSCs: Liver cancer stem cells; CTCs: Circulating tumor cells; lncRNAs: Long non-coding RNAs; CircRNAs: Circular RNAs; miRNAs: MicroRNAs.