Biomarkers of gastric cancer: Current topics and future perspective

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.