Table 1.
Current topics of molecular markers associated with diagnosis, prognosis, prediction of therapeutic response of gastric cancer
| Marker | Alteration | Clinical purpose | Detection method | Ref. |
| Metastasis related genes | ||||
| Growth factors | ||||
| HER2, FGFR, PI3K/Akt/mTOR (PIK3CA), MET, VEGF (VEGFR-2, VEGF-D) | Overexpression | Diagnostic/prognostic/therapeutic | Tissue | [16-18,25,32,33, 44-46,55,58] |
| Cell cycle regulation | ||||
| TP53 | Mutation | Diagnostic | Tissue | [60,61,63] |
| Adhesion molecule | ||||
| E-cadherin (CDH1) | Mutation/epigenetic alteration | Diagnostic/prognostic | Tissue/blood | [39,40] |
| Immune checkpoint | ||||
| PD-L1 | Mutation | Prognostic/therapeutic | Tissue | [66,67] |
| Comprehensive gene analysis | ||||
| CEACEM6, APOC1, YF13H12, CDH17, REG4, OLFM4, HOXA10, DSC2, TSPAN8, TM9SF3, FUS, COLIA1, COLIA2, APOE | Up-regulated | Diagnostic/prognostic/therapeutic | Tissue | [74,75] |
| ATP4B, S100A9, CYP20A1, ARPC3, DDX5 CLDN18 | Down-regulated | Diagnostic/prognostic/therapeutic | Tissue | [74,75] |
| Microsatellite instability | High level | Prognostic/therapeutic | Tissue | [79,81,82] |
| Epigenetic alterations | ||||
| CDH1, CHFR, DAPK, GSTP1, p15, p16, RARβ, RASSF1A, RUNX3, TFPI2 | Hypermethylation | Diagnostic | Tissue | [84-86] |
| Genetic polymorphism | ||||
| IL1-β, IL-1RN, CD44 | SNP | Prognostic | Tissue | [89,90] |
| TP53, SYNE1, CSMD3, LRP1B, CDH1, PIK3CA, ARID1A, PKHD, KRAS, JAK2, CD274, PDCD1LG2 | Copy number variations/mutations | Diagnostic/prognostic/therapeutic | Tissue | [91,92] |
| Circulating tumor cells | ||||
| CD44, N-cadherin, vimentin | Overexpression | Diagnostic/therapeutic | Blood | [96] |
| pan-CK, E-cadherin | Decreased expression | EMT process | Blood | [97] |
| HER2 | Overexpression | Therapeutic | Blood | [99] |
| Circulating cell-free DNA | ||||
| APC promotor 1, RASSF1A | Hypermethylation | Diagnostic | Blood/plasma | [102] |
| ERBB2 | Copy number variations | Therapeutic | Plasma | [26] |
| MicroRNA | ||||
| miR-21, miR-23a, miR-27a, miR-106b-25, miR-130b, miR-199a, miR-215, miR-222-221, miR-370 | Up-regulated | Diagnostic/prognostic/therapeutic | Blood/plasma | [108,111] |
| miR-29a, miR-101, miR-125a, miR-129, miR-148b, miR-181c, miR-212, miR-218, miR-335, miR-375, miR-449, miR-486, miR-512 | Up-regulated | Diagnostic/prognostic/therapeutic | Blood/plasma | [108,111] |
| Cell-free miRNAs | ||||
| miR-331 and miR-21 | Up-regulated | Diagnostic/Prognostic | Blood | [113] |
| miR-20b, 125a, 137, 141, 146a, 196a, 206, 218, 486-5p | Up-regulated | Prognostic | Blood/plasma | [114] |
| miR10b-5p, miR132-3p, miR185-5p, miR195-5p, miR-20a3p, miR296-5p | Up-regulated | Prognostic | Plasma | [115] |
| Long noncoding RNAs | ||||
| ncRuPAR | Down-regulated | Diagnostic/prognostic | Tissue | [119] |
| AI364715, GACAT1, GACAT2 | Down-regulated | Prognostic | Tissue | [120] |
| PVT1 | Up-regulated | Prognostic | Tissue | [121] |
| Exosomes | ||||
| MiR-19b, miR-106a | Up-regulated | Diagnostic/prognostic | Plasma | [129] |
| miR-21, miR-1225-5p | Up-regulated | Diagnostic/therapeutic | PLF | [130] |
| Stomach specific biomarker | ||||
| ADAM23, GDNF, MINT25, MLF1, PRDM5, RORA | Hypermethylation | Diagnostic | Gastric wash | [131] |
| BARHL2 | Hypermethylation | Diagnostic/therapeutic | Gastric wash/juice | [132] |
| PVT1 | Up-regulated | Diagnostic/prognostic | Gastric juice | [121] |
| miR-421, miR-21, miR-106a, miR-129 | Up-regulated | Diagnostic | Gastric juice | [133] |
| CagA | Up-regulated | Diagnostic | Tissue | [137] |
| VacA | Up-regulated | Diagnostic | Tissue | [138] |
| Gastrokine 1 | Inactivation | Prognostic | Tissue | [139] |
HER2: Human epidermal growth factor receptor 2; PLF: Peritoneal lavage fluid; FGFR: Fibroblast growth hormone receptor; PI3K: Phosphatidylinositol-3-kinase; mTOR: Mechanistic target of rapamycin; VEGF: Vascular endothelial growth factor; PD-1L: Programmed death-1 ligands; MSI: Microsatellite instability; CagA: Cytotoxin-associated gene A; VacA: Vacuolating toxin A.