Table 2.
The roles and functions of signaling pathways in gastric cancer, and the identified biomarkers as well as potential therapeutic targets
| Signaling pathways | Roles and functions | Biomarkers and potential therapeutic targets | |
|---|---|---|---|
| Significant roles in GC | Cellular Biological Processes | ||
| MAPK signaling pathway | Prognosis biomarker and related to chemotherapy resistance | Growth, proliferation, differentiation, migration, invasion, metastasis, apoptosis, ROS, cell cycle | CLDN18.2, RTKs, ERK, p-ERK, JNK, p-JNK, p38-MAPKs, p-p38-MAPKs, MEK, p-MEK, RAS, RAF, miR29, miR181c, miR-939, miR-592, lncRNA-MALAT1, lncRNA-CASC2 |
| HER2 signaling pathway | Prognosis biomarker and related to tumor recurrence | Proliferation, differentiation, migration, survival, metastasis, angiogenesis | EGFR, HER2/3/4, ERK, p-ERK, PTEN |
| PI3K/AKT/mTOR signaling pathway | Diagnosis and prognosis biomarker, related to chemotherapy resistance | Proliferation, survival, migration, invasion, metastasis, cell cycle, apoptosis, angiogenesis | RTKs, PI3K, AKT, p-AKT, mTOR, p-mTOR, PTEN, mTORC1/2, p70S6K1, GSK3, PDK1 |
| P53 signaling pathway | Prognosis biomarker, related to tumor recurrence and chemotherapy resistance | Proliferation, differentiation, metastasis, cell cycle, apoptosis, immune response, inflammation | CDK, RPRM, p21, p16, TP53INP1, USF1/2, miR-17-5p, miR-20a, miR-181a, miR-449, miR-650 |
| HGF/c-MET signaling pathway | Prognosis biomarker, related to chemotherapy resistance | Proliferation, survival, hypoxia, migration, invasion, metastasis, cell cycle, apoptosis, inflammation | RAS, HPA, CXCL12, CXCR4, miR-15a/16/195 |
| Wnt/β-catenin signaling pathway | Diagnosis and prognosis biomarker, related to tumor recurrence and chemotherapy resistance | ROS, proliferation, differentiation, survival, cell cycle, apoptosis, migration, invasion, immune response | TCF4, Gpx4, CCL28 |
| NF-κB signaling pathway | Related to tumor recurrence, chemotherapy resistance and radioresistance | Proliferation, survival, invasion, angiogenesis, metastasis, cell cycle, apoptosis, inflammation | Bcl-2, BIRC5, TRAF, COX-2, MMP-9, iNOS, CCND1 |
| TGF-β signaling pathway | Prognosis biomarker, related to tumor recurrence | Proliferation, differentiation, metastasis, apoptosis, immune response | SMAD, AMPK |
| PD-1 signaling pathway | Prognosis biomarker, related to immuno tolerance | Proliferation, survival, metastasis, apoptosis, immune response | PD-L1/PD-L2, IFN-γ, miR-105-5p |
| CD28/CTLA-4/B7 signaling pathway | Immune response | CTLA-4, B7-1/2 | |
| TIM-3, LAG-3, TIGIT signaling pathway | Prognosis biomarker, related to tumor recurrence and immune tolerance | Apoptosis, immune response | Galectin-9, galectin-3, CD-155, CD112 |
| FGFR signaling pathway | Diagnosis and prognosis biomarker | Proliferation, differentiation, angiogenesis, migration, invasion, metastasis | RAS, JAK, YAP, miR-590-5p |
| STAT3 signaling pathway | Diagnosis and prognosis biomarker, related to chemotherapy resistance | Proliferation, invasion, metastasis | IL-6, JAK, EZH2, survivin, miR-125b-5p, miR-143, miR-375, miR-3619-5p, circVAPA |
| HIF-1α signaling pathway | Related to chemotherapy resistance | Proliferation, survival, angiogenesis, metastasis, cell apoptosis, hypoxia, metabolism, inflammation | NDRG, CXCR4, LXR, RhoE, HIF-1α/microRNAs, HIF-1α/lncRNAs |
| Hedgehog signaling pathway | Prognosis biomarker | Proliferation, differentiation, cell cycle | PTCH1, FOXM1, CCND2 |
| Notch signaling pathway | Related to tumor recurrence | Proliferation, differentiation, survival, migration, invasion, metastasis | Jagged1, DLL4, Hes1 |
MAPK mitogen-activated protein kinase, ROS reactive oxygen species, CLDN18 Claudin 18, RTK receptor tyrosine kinases, ERK extracellular signal-regulated kinases, JNK c-Jun N-terminal kinases, MEK mitogen-activated protein kinase kinase, RAS rat sarcoma virus, RAF rapidly accelerated fibrosarcoma, CASC2 cancer susceptibility 2, EGFR epidermal growth factor receptor, HER2/3/4 human epidermal growth factor receptor 2/3/4, PTEN phosphatase and tensin homolog, PI3K phosphoinositide 3-kinase, AKT protein kinase B, mTOR mammalian target of rapamycin, mTORC1/2 mammalian target of rapamycin complex 1/2, GSK3 glycogen synthase kinase 3, PDK pyruvate dehydrogenase kinase, CDK cyclin-dependent kinases, RPRM reprimo, TP53 tumor protein p53, USF1/2 upstream stimulatory factor 1/2, HPA human protein atlas, CXCL12 CXC motif chemokine 12, CXCR4 CXC chemokine receptor type 4, TCF4 transcription factor 4, Gpx4 glutathione peroxidase 4, CCL28 chemokine ligand 28, Bcl-2 B-cell lymphoma 2, BIRC5 baculoviral inhibitor of apoptosis repeat-containing 5, TRAF tumor necrosis factor receptor associated factors, COX-2 prostaglandin-endoperoxide synthase 2, MMP-9 matrix metallopeptidase 9, iNOS cytokine inducible nitric oxide synthases, CCND1 cyclin D1, SMAD suppressor of mothers against decapentaplegic, AMPK 5′ adenosine monophosphate-activated protein kinase, PD-L1/PD-L2 programmed death-ligand 1/2, IFN-γ interferon gamma, CTLA-4 cytotoxic T-lymphocyte-associated protein 4, TIGIT T cell immunoreceptor with Ig and ITIM domains, TIM-3 T cell immunoglobulin and mucin-domain containing-3, LAG-3 lymphocyte-activation gene 3, JAK janus kinase, YAP yes-associated protein 1, IL-6 interleukin 6, EZH2 enhancer of zeste homolog 2, VAPA vesicle-associated membrane protein-associated protein A, NDRG N-myc downregulated gene, LXR liver X receptor, RhoE rho-related guanosine-5′-triphosphate-binding protein, PTCH1 protein patched homolog 1, FOXM1 forkhead box protein M1, CCND2 cyclin D2, DLL4 delta-like 4, Hes1 hairy and enhancer of split-1