Potential prognostic, diagnostic and therapeutic markers for human gastric cancer

Table 1 Serum-based tumor markers in gastric cancer

Biological category	Biomarker (Gene name)	Cutoff level /Expression levels in human GC serum	Clinical significance	Associated tumor types	Ref.
Oncofetal antigen	CEA	5 μg/L	Prognosis	Gastrointestinal cancer	[24,25]
			GC progression monitoring	Cervix cancer
				Lung cancer
				Ovary cancer
				Breast cancer
				Urinary tract cancer
Glycoprotein antigen	CA19.9	37 kU/L	Prognosis	Mainly pancreatic cancer	[26]
			GC progression	but also colorectal cancer
			monitoring	other types of gastrointestinal cancer
	CA72.4	6 kU/L	Prognosis	Ovary cancer	[27]
			GC progression	Breast cancer
			monitoring	Colon cancer
				Pancreatic cancer
Cytokeratins	Cyfra21.1	Variable	Prognosis	Many types of carcinoma	[29]
				Some types of sarcoma
	TPA	Variable	Prognosis	Carcinoma	[30]
	TPS	Variable	Prognosis	Adult epithelial tumours	[30]
Hormone	Β subunit of hCG	4 μg/L	Prognosis	Seminoma	[31]
				Choriocarcinoma
				Germ cell tumors
				Choriocarcinoma
				Islet cell tumor
				Testicular cancer
Cell proliferation	Reg IV	Overexpression	Prognosis	Gastrointestinal malignancies	[33,34]
	Granulin	Overexpression	Prognosis	Gastrointestinal malignancies	[35,36]
Signaling protein	14-3-3 protein	Downexpression	Prognosis	Epithelial cancer	[40-42]
				Lung cancer
				Breast cancer
				Bladder cancer
				Liver cancer
				Oral cancer
				Head-and-neck squamous cell cancer
	DKK-1	Overexpression	Prognosis	Prostate cancer	[43-49]
				Breast cancer
				Colon cancer
				Esophageal cancer
				Lung cancer
				Multiple myeloma (MM)
Inflammatory	SAA	Overexpression	Prognosis	Lung cancer	[50,52,53]
				Kidney cancer
				Colon cancer
				Prostate cancer
				Liver cancer
Cell apoptosis	MG7-Ag	Overexpression	Prognosis	Gastrointestinal cancer	[55,56]
Enzyme	PG	Overexpression	Prognosis	Gastrointestinal cancer	[57]

CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; CA72-4: Carbohydrate antigen 72-4; Cyfra21.1: Cytokeratin subunit 19 fragment; TPA: Tissue polypeptide antigen; TPS: Tissue polypeptide-specific antigen; β-hCG: β-subunit of human chorionic gonadotropin; Reg IV: Regenerating gene IV; Dkk-1: Dickkopf-1; SAA: Serum Amyloid A; MG7-Ag: Gastric cancer associated antigen; PG: Pepsinogens.

Table 2 Tissue-based tumor markers in gastric cancer

Biological category	Biomarker (Gene name)	Parameters	Clinical significance	Associated tumor types	Ref.
Receptor	HER2/neu	Lauren histotype	Prognosis	Ovarian cancer	[58-63]
		Lymph node metastasis	Therapeutic response	Stomach cancer
				Uterine cancer
				Endometrial cancer
				Breast cancer
				Esophageal cancer
	VEGF	Lauren histotype	Prognosis	Breast cancer.	[64-68]
		Tumor progression	Therapeutic response	Colon cancer
				Gastric cancer
				Liver cancer
				Lung cancer
Ion channel	hERG1	Lauren histotype	Prognosis	Endometrial cancer	[69]
		Grading		Gastric cancer
		Stage		Colorectal cancer
Transcription factor	KLF5/IKLF/BTEB2	Grading	Prognosis	Bladder cancer	[71,72]
		Stage		Prostate cancer
		Lymph node status		Breast cancer
				Colon cancer
	SATB1	Lymph node metastasis	Prognosis	Breast cancer	[75-78]
		Distant metastasis		Gastric cancer
		Stage		Colon cancer
				Bladder cancer
	c-myc2	Lymph node metastasis	Prognosis	Cervix cancer	[80]
				Colon cancer
				Breast cancer
				Lung cancer
				Stomach cancer
Enzyme	CA IX	Lymph node metastasis	Prognosis	Kidney cancer	[81-83]
				Colon cancer
				Cervical cancer
	MMP-2	Stage	Prognosis	Ovarian cancer	[79,80,84,85]
		Survival		Colon cancer
				Breast cancer
				Bladder cancer
				Gastric cancer
	HDAC	Lymph node metastasis	Prognosis	Renal cancer	[86-92]
		Survival		Colorectal cancer
				Gastric cancer
				Breast cancer
				Pancreatic cancer
				Liver cancer
				Lung cancer
				Prostate cancer
				Hodgkin's lymphoma
	COX-2	Lymph node metastasis	Prognosis	Breast cancer	[93,94]
		Survival		Intestinal tract cancer
	SLPI	Depth of invasion	Prognosis	Ovan cancer	[96,97]
		Serosal invasion		Cervical cancer
		Lymph node metastasis		Gastric cancer
		Stage
	GLO1	Depth of invasion	Prognosis	Colon cancer	[99-103]
		Serosal invasion		Breast cancer
		Lymph node metastasis		Prostate cancer
		Stage		Gastric cancer
				Melanoma cancer
Cell growth	Ki-67	Lymph node metastasis	Prognosis	Prostate cancer	[104]
				Brain cancer
				Breast cancer
				Nephroblastoma
	TGF-β	Stage	Prognosis	Breast cancer	[105,106]
				Gastric cancer
Signal	PKP3	Stage	Prognosis	Gastric cancer	[109,110]
Protein/cell adhesion				Lung cancer
	E-cadherin	Invasion	Prognosis	Esophagus cancer	[111]
		Grading		Ovary cancer
		Lauren histotype		Stomach cancer
	TSP-1	Stage	Prognosis	Breast cancer	[112-115]
				Melanoma cancer
				Lung cancer
				Gastric cancer
	SPARC	Depth of invasion	Prognosis	Breast cancer	[118-120]
		Serosal invasion		Melanoma cancer
		Lymph node metastasis		Gastric cancer
		Distant metastasis		Oesophageal cancer
				Glioma cancer
Regulate cell death (apoptosis)	Bcl-2	Lymph node metastasis	Prognosis	Melanoma cancer	[121]
				Breast cancer
				Prostate cancer
				Chronic lymphocytic Leukemia lung cancer
	Bcl-6	Lymph node metastasis	Prognosis	Gastric cancer	[122]
				Pancreas cancer
				Colon cancer
				Bladder cancer
	Bax	No data	Prognosis	Gastric cancer	[123-125]
				Colon cancer
Cytokine	CXCL1/CXCR2	Lymph node metastasis	Prognosis	Gastric cancer	[128]
				Colon cancer
Vesicular transport	ARF1	Depth of invasion	Prognosis	Gastric cancer	[129]
		Serosal invasion
		Lymph node metastasis
		Distant metastasis
		Stage

HER2/neu: Human epidermal growth factor receptor 2/neu; VEGF: Vascular endothelial growth factor; hERG1: Human Ether-à-go-go-Related Gene; KLF5/IKLF/BTEB2: Krueppel-like factor 5; SATB1: Special AT-rich sequence-binding protein-1; CA IX: Carbonic anhydrase 9; MMP-2: Matrix metalloproteinase-2; HDAC: Histone deacetylases; SLP1: Antiprotease secretory leukocyte protease inhibitor; GLO1: Glyoxalase I; TGF-β: Transforming growth factor beta; PKP3: Plakophilin-3; TSP-1: Thrombospondin 1; SPARC: Secreted protein and rich in cysteine; Bcl-2: B-cell lymphoma 2; Bcl-6: B-cell lymphoma 6; Bax: Bcl-2-associated X protein; CXCL1: Chemokine (C-X-C motif) ligand 1; CXCR2: CXC chemokine receptors 2; ARF1: ADP-ribosylation factor 1.